Systems and methods for multiple layer intraocular lens and using refractive index writing

ABSTRACT

Systems and methods for improving vision of a subject implanted with an intraocular lens (IOL). In some embodiments, a method includes determining at least one modification to be made to an IOL implanted in a subject to improve the vision of the subject, wherein the IOL has a first index of refraction; and based on the determination, applying laser radiation to at least one selected area of the IOL to form, within the IOL, at least one additional layer having a different index of refraction than the first index of refraction and a particular shape within the IOL configured to improve the vision of the subject.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit under 35 U.S.C. § 119(e) of U.S.Provisional Patent Application No. 62/830,312, filed Apr. 5, 2019, whichis incorporated herein by reference in its entirety.

BACKGROUND

Currently a range of factors can limit visual performance of a patient(also referred to herein as a “subject”) following corrective surgery(e.g., cataract surgery) in which an intraocular lens (IOL) is implantedin the patient's eye(s). These limiting factors can include: incorrectIOL power, which is commonly caused by incorrect IOL power calculationsdue to biometry accuracy; and uncorrected astigmatism, which can becaused by factors such as surgically induced astigmatism, effect ofposterior corneal astigmatism, incorrect toric IOL power calculation,toric IOL rotation, or misplacement and use of non-toric IOLs in toriccorneas. Additional limiting factors can include: spectacle dependence,which can be due to monofocal IOL implantation, as well as incorrectestimations of the most suitable presbyopia correcting IOLs for thepatient; photic phenomena, such as halos, starburst and glare, forexample in patients using presbyopia-correcting IOLs; negativedysphotopsia; peripheral aberration, and chromatic aberration. Replacingan implanted IOL that causes negative post-surgical visual outcomes fora patient can be a risky and complicated procedure. Therefore, amongother needs, there exists a need to alleviate negative post-surgicalvisual outcomes without the need of IOL replacement.

SUMMARY

Among other aspects, certain embodiments of the present disclosurerelate to improving vision in a subject with an implanted intraocularlens (IOL) without the need to replace the IOL, through the use ofrefractive index writing (MW).

In one aspect, the present disclosure relates to a method for improvingvision in a subject having an implanted intraocular lens (IOL), which inone embodiment can include determining at least one modification to bemade to an IOL implanted in a subject to improve the vision of thesubject, wherein the IOL has a first index of refraction. The method canalso include, based on the determination, applying laser radiation to atleast one selected area of the IOL to form, within the IOL, at least oneadditional layer having a different index of refraction than the firstindex of refraction and a particular shape within the IOL configured toimprove the vision of the subject.

In some embodiments, the applied laser radiation changes the index ofrefraction of the at least one selected area from the first refractiveindex to the different index of refraction in forming the at least oneadditional layer. The index of refraction of the at least one additionallayer can be uniform throughout the respective layer. The at least oneadditional layer can be formed with a series of transitions within theIOL and/or formed to have a shape defined by portions having differentdepths within the IOL. The at least one additional layer can be formedto have a particular thickness and, when formed, at least one of thelayers has a different thickness than another one of the layers.

In some embodiments, applied laser radiation can include one or moreselected optical energies focused in the at least one selected area andone or more selected durations of exposure of the focused optical energyin the at least one selected area, determined at least in part based onthe determined at least one modification to be made to the IOL. In someembodiments, the at least one additional layer can include more than twoadditional layers, and each of the more than two additional layers canhave a respective index of refraction and be formed with a particularshape within the IOL. The more than two additional layers can include atleast two different shapes.

In some embodiments, the at least one modification to be made to the IOLcan correspond to correcting at least one of incorrect IOL power,uncorrected astigmatism, IOL placement error, higher order aberration,spectacle dependence, negative dysphotopsia, peripheral aberrations, andchromatic aberrations. Applying the laser radiation can include indexwriting with a plurality of focused laser pulses applied to the at leastone selected area of the IOL according to a predetermined pattern. Thepredetermined pattern can be based at least in part on the determined atleast one modification to be made to the IOL.

In another aspect, in some embodiments a method for forming amulti-layered intraocular lens (IOL) can include determining at leastone modification to be made to an IOL to improve the visual performanceof the IOL, where the IOL has a first index of refraction and, based onthe determination, applying laser radiation to the IOL to form, withinthe IOL, at least one additional layer having a different index ofrefraction than the first index of refraction and a particular shapewithin the IOL configured to improve the visual performance of the IOL.

The applied laser radiation can change the index of refraction of the atleast one selected area from the first refractive index to the differentindex of refraction in forming the at least one additional layer. Theindex of refraction of the at least one additional layer can be uniformthroughout the respective layer. The at least one additional layer canbe formed to have a shape defined by portions having different depthswithin the IOL, wherein at least one of the layers has a differentthickness than another one of the layers.

In some embodiments, the applied laser radiation can include one or moreselected optical energies focused in the at least one selected area ofthe IOL and one or more selected durations of exposure of the focusedoptical energy in the at least one selected area, determined at least inpart based on the determined at least one modification to be made to theIOL. Applying the laser radiation can include refractive index writingwith a plurality of laser pulses applied to the at lease one selectedarea of the IOL according to a predetermined pattern. The predeterminedpattern can be based at least in part on the determined at least onemodification to be made to the IOL.

In yet another aspect, in some embodiments a system for improving visionof a subject can include at least one sensor configured to determine acorrection to be made to an intraocular lens (IOL) to improve the visionof a subject, wherein the IOL has a first index of diffraction. Thesystem can also include a control system operatively coupled to the atleast one sensor and configured to receive associated sensed datacorresponding to the correction to be made to the IOL and to calculate,based on the sensed data, shape and/or index of refraction for at leastone additional layer to be formed within the IOL. The additional layercan have a different index of refraction than the first index ofrefraction and a particular shape within the IOL configured to improvethe vision of the subject. Additionally or alternatively, the controlsystem can calculate parameters for a pattern of laser radiation to beapplied to at least one selected area of the IOL to form the at leastone additional layer; and a radiation system operatively coupled to thecontrol system and configured to, based on control by the controlsystem, apply focused laser radiation according to the parameters andpattern of laser radiation to be applied to at least one selected areaof the IOL, to form, within the IOL, the at least one additional layerhaving the different index of refraction and the particular shape.

The calculated parameters for the pattern of laser radiation can includeone or more selected optical energies to be focused in the at least oneselected area and one or more selected durations of exposure for thefocused optical energy in the at least one selected area. The radiationsystem can be a pulsed laser system configured to apply the laserradiation by refractive index writing with a plurality of focused laserpulses applied to IOL according to the calculated parameters andpattern.

In some embodiments, the at least one sensor corresponds to an opticalcoherence tomography (OCT) system configured to determine biometric dataassociated with the correction to be made to the IOL. The applied laserradiation can change the index of refraction of the at least one area ofthe IOL from the first refractive index to the different index ofrefraction in forming the at least one additional layer. The index ofrefraction of the formed at least one additional layer can be uniformthroughout the respective layer. The at least one additional layer canbe formed with a series of transitions within the IOL. The at least oneadditional layer can be formed to have a shape defined by portionshaving different depths within the IOL. The at least one additionallayer can be formed to have a particular thickness, and wherein, whenformed, at least one of the layers can have a different thickness thananother one of the layers.

Other aspects and features according to the present disclosure willbecome apparent to those of ordinary skill in the art, upon reviewingthe following detailed description in conjunction with the accompanyingfigures.

BRIEF DESCRIPTION OF THE DRAWINGS

Reference will now be made to the accompanying drawings, which are notnecessarily drawn to scale. Like reference numerals designatecorresponding parts throughout the several views.

FIG. 1A illustrates a side view of an eye containing a natural lens.

FIG. 1B illustrates a side view of the eye shown in FIG. 1A with animplanted intraocular lens (IOL).

FIG. 2 is a schematic diagram of an example optical system capable ofimplementing one or more aspects of the present disclosure in accordancewith various embodiments.

FIG. 3 shows is a diagram of an example computing system capable ofperforming various functions in accordance with one or more aspects andembodiments of the present disclosure.

FIG. 4 illustrates phase addition of a presbyopia-correcting IOL and thephase addition needed to be introduced, by refractive index writing, toremove unwanted visual symptoms, in accordance with some embodiments ofthe present disclosure.

FIG. 5A is an illustration of an IOL tilted with respect to the opticalaxis OA, and FIG. 5B is an illustration of an IOL decentered withrespect to the optical axis OA.

FIG. 6A illustrates a phase map (in waves of a 20 D monofocal IOLimplanted in an average eye. FIG. 6B illustrates the phase map (inwaves) induced by 5 degrees tilt of a 20 D monofocal IOL. FIG. 6Cillustrates the phase map (in waves) induced by 0.5 mm decentration of a20 D monofocal IOL.

FIG. 7 plots the residual of a conventional phase profile with step sizelager than a wavelength and its corresponding wrapped profile, inaccordance with some embodiments of the present disclosure.

FIGS. 8A-8C illustrate various aspects of phase wrapping in accordancewith some embodiments of the present disclosure.

FIGS. 9A and 9B illustrate aspects of vergence matching in accordancewith some embodiments of the present disclosure.

FIGS. 10A-10C illustrate aspects of vergence matching with refractiveindex writing designs, in accordance with embodiments of the presentdisclosure.

FIGS. 11 and 12 illustrate the radial dependence of the refractive indexchange for different thicknesses of the optical profile written insidethe IOL, for power subtraction (FIG. 11) and power addition (FIG. 12),in accordance with embodiments of the present disclosure.

FIGS. 13 and 14 illustrate the radial dependence of the refractive indexchange for different thicknesses of the optical profile written insidethe IOL for spectacle independence, for negative added power (FIG. 13)and positive added power (FIG. 14), in accordance with embodiments ofthe present disclosure.

FIG. 15 shows results of simulations in TCEM illustrating throughfrequency MTF with a comparison between an IOL with a refractiveanterior and posterior surface (“refractive”), an IOL with refractiveindex writing without vergence matching (“grin_standard”), and an IOLwith vergence matching according to some embodiments of the presentdisclosure (“refractive_grin_with_vergence_matching”).

FIGS. 16 and 17 show the results of simulations in TCEM illustratingthrough frequency MTF (FIG. 16) and through focus MTF at 50 c/mm (FIG.17), with a comparison between an IOL with a refractive anterior andposterior surface (“refractive”), an IOL with refractive index writingwithout vergence matching (“grin_standard”), an IOL like thegrin_standard, but with the refractive index shrunk along the z axis inaccordance with vergence matching in some embodiments described above(“grin_shrink”), and an IOL with refractive anterior and diffractive,elevated, posterior surface according to conventional diffractive IOLs(“diffractive sag”).

FIGS. 18 and 19 show results illustrating a similar comparison fornormalized polychromatic PSF (FIG. 18) and polychromatic halo simulation(FIG. 19).

FIG. 20 shows simulated halo performance for a number of differentdesigns: that of a standard refractive IOL (“refractive”), that of anextended depth of focus embodiment with vergence matching (“grinshrink”), that of an extended depth of focus embodiment IOL implementedwith normal refractive index writing (“grin standard”), and the sameextended depth of focus embodiment achieved by standard methods ofelevated posterior surface (“diffractive sag”).

FIG. 21 illustrates an IOL with multiple layers produced by refractiveindex writing according to some embodiments of the present disclosure.

DETAILED DESCRIPTION

Among other aspects, certain embodiments of the present disclosurerelate to improving vision in a subject with an implanted intraocularlens (IOL) through the use of refractive index writing on the IOL.Refractive index writing (RIW) as described herein can utilize shortpulses of focused irradiation focused on a selected area of an IOL inorder to change the refractive index of the selected area and therebymodify optical performance of the IOL to correct post-surgical visionproblems of the subject. For example, short and focused pulses ofradiation from a visible or near-IR laser with a sufficient pulse energycan cause a nonlinear absorption of photons and lead to a change in therefractive index of the material at a focus point (in the selected areaof the IOL) without affecting areas of the IOL outside of the selectedarea. Optical parameters of the pulsed radiation applied to the IOL,including the wavelength, pulse duration, frequency, and/energy can beconfigured to produce, by the refractive index writing, correctivepatterns and/or structures on selected areas of the IOL to correct,e.g., to introduce a phase shift and modify the phase profile, of one ormore portions of the IOL to improve vision in a subject. The patternaccording to which the pulses of radiation are applied can be in theform of a determined pulse sequence, for example, with the opticalparameters as mentioned above incorporated

According to some embodiments of the present disclosure, the startingpoint of a desired refractive index implementation is a phase map thathas been shown to, for example, shift power, reduce residualastigmatism, improve near vision, improve spectacle independence, orreduce visual symptoms, among other undesired vision conditions andeffects as described herein with respect to various embodiments. In someembodiments according to the present disclosure, calculations such asestimates and/or various measurements may be utilized in determining(e.g., designing) a phase map that corresponds to a pattern or otherelement(s) to be produced on a selected area (e.g., surface, interiorportion) of an IOL in order to correct unwanted visual conditions and/oreffects and reach a desired result in the modified IOL design. Inaccordance with some embodiments, a voxel-based treatment of the IOL isapplied, wherein as one goes sequentially through each voxel, thedesired shift in refractive index is applied, determined by total amountof light energy focused in the particular area and the duration of focustime.

Although example embodiments of the present disclosure are explained indetail herein, it is to be understood that other embodiments arecontemplated. Accordingly, it is not intended that the presentdisclosure be limited in its scope to the details of construction andarrangement of components set forth in the following description orillustrated in the drawings. The present disclosure is capable of otherembodiments and of being practiced or carried out in various ways.

It must also be noted that, as used in the specification and theappended claims, the singular forms “a,” “an” and “the” include pluralreferents unless the context clearly dictates otherwise. By “comprising”or “containing” or “including” is meant that at least the namedcompound, element, particle, or method step is present in thecomposition or article or method, but does not exclude the presence ofother compounds, materials, particles, method steps, even if the othersuch compounds, material, particles, method steps have the same functionas what is named.

In describing example embodiments, terminology will be resorted to forthe sake of clarity. It is intended that each term contemplates itsbroadest meaning as understood by those skilled in the art and includesall technical equivalents that operate in a similar manner to accomplisha similar purpose. It is also to be understood that the mention of oneor more steps of a method does not preclude the presence of additionalmethod steps or intervening method steps between those steps expresslyidentified. Steps of a method may be performed in a different order thanthose described herein without departing from the scope of the presentdisclosure. Similarly, it is also to be understood that the mention ofone or more components in a device or system does not preclude thepresence of additional components or intervening components betweenthose components expressly identified.

Ranges may be expressed herein as from “about” one particular value,and/or to “about” another particular value. When such a range isexpressed, an aspect includes from the one particular value and/or tothe other particular value. Similarly, when values are expressed asapproximations, by use of the antecedent “about,” it will be understoodthat the particular value forms another aspect. It will be furtherunderstood that the endpoints of each of the ranges are significant bothin relation to the other endpoint, and independently of the otherendpoint. As discussed herein, a “subject” or“patient” refers to anyapplicable human, animal, or other organism and may relate to specificcomponents of the subject, in particular the eye of the subject and anyapplicable components such as various related muscles, tissues, and/orfluids.

As used herein, the term “optical power” of a lens or optic means theability of the lens or optic to converge or diverge light to provide afocus (real or virtual), and is specified in reciprocal meters orDiopters (D). As used herein the terms “focus” or “focal length” of alens or optic is the reciprocal of the optical power. As used herein theterm “power” of a lens or optic means optical power. Except where notedotherwise, optical power (either absolute or add power) of anintraocular lens or associated optic is from a reference planeassociated with the lens or optic (e.g, a principal plane of an optic).

As used herein, the term “near vision” means vision produced by an eyethat allows a subject to focus on objects that are at a distance of, forexample 40 cm or closer to a subject, such as within a range of 25 cm to33 cm from the subject, which corresponds to a distance at which asubject would generally place printed material for the purpose ofreading. As used herein, the term “intermediate vision” means visionproduced by an eye that allows a subject to focus on objects that arelocated, for example, between 40 cm and 2 meters from the subject. Asused herein, the term “distant vision” means vision produced by an eyethat allows a subject to focus on objects that are, for example at adistance that is greater than 2 meters, such as at a distance of about 5meters from the subject, or at a distance of about 6 meters from thesubject, or greater.

Various aspects of the present disclosure will now be described,including aspects and embodiments discussed with reference to someexample implementations and corresponding results, and the illustrationsof FIGS. 1-21. Some experimental data are presented herein for purposesof illustration and should not be construed as limiting the scope of thepresent disclosure in any way or excluding any alternative or additionalembodiments.

Referring now to FIG. 1A, a cross-sectional view of a pseudo-phakic eye10 containing the natural lens is shown, in which eye 10 includes aretina 12 that receives light in the form of an image produced whenlight from an object is focused by the combination of the optical powersof a cornea 14 and a natural lens 16. The cornea 14 and lens 16 aregenerally disposed about an optical axis (OA). As a general convention,an anterior side is considered to be a side closer to the cornea 14,while a posterior side is considered to be a side closer to the retina12.

The natural lens 16 is enclosed within a capsular bag 20, which is athin membrane attached to a ciliary muscle 22 via zonules 24. An iris26, disposed between the cornea 14 and the natural lens 16, provides avariable pupil that dilates under lower lighting conditions (mesopic orscotopic vision) and constricts under brighter lighting conditions(photopic vision). The ciliary muscle 22, via the zonules 24, controlsthe shape and position of the natural lens 16, allowing the eye 10 tofocus on both distant and near objects. It is generally understood thatdistant vision is provided when the ciliary muscle 22 is relaxed,wherein the zonules 24 pull the natural lens 16 so that the capsular bag20 and lens 16 are generally flatter and provide a longer focal length(lower optical power). It is generally understood that near vision isprovided when the ciliary muscle contracts, thereby relaxing the zonules24 and allowing the capsular bag 20 and lens 16 to return to a morerounded state that produces a shorter focal length (higher opticalpower).

Referring now to FIG. 1B, a cross-sectional view of an eye 10′ is shownin which the natural crystalline lens 16 has been replaced by anintraocular lens (IOL) 100 according to one or more embodimentsdisclosed herein. The intraocular lens 100 can include an optic 102 andhaptics 103, the haptics 103 being configured to at least generallycenter the optic 102 within the capsular bag 20, provide transfer ofocular forces to the optic 102, and the like. Numerous configurations ofhaptics 103 relative to optic 102 are well known within the art, and theoptics edge designs described herein can generally include any of thesehaptic configurations. Moreover, this disclosure contemplates that themethods described herein can be used to evaluate any IOL independentlyof the haptics configuration and/or optics design.

Refractive Index Writing System

FIG. 2 shows example of a system 200 capable of implementing one or moreaspects of the present disclosure in accordance with various embodimentsdescribed in further detail throughout the present description. Theexample system of FIG. 2 includes a pulsed radiation system 202including a light source configured to emit radiation such as laserpulses, a control system 204, a relay unit 206, eye with an implantedIOL 208, and sensors 210.

In some embodiments, the light source of the pulsed radiation system 202can be a femtosecond laser operating in the visible or near-infraredwavelength range, and pulsed according to a sequence (i.e.,predetermined pattern of laser pulses having particular opticalparameters as mentioned in some examples described below) configured toproduce a desired change in the IOL 208. As some non-limiting examples,the optical parameters can include, for the emitted laser radiationpulses, a Gaussian or clipped beam profile, spot spacing between about0.1 and 5 microns, and a pulse energy of up to about 500 nJ per pulse.

In some embodiments, sensors 210 can include an optical coherencetomography (OCT) system for determining, for example, the IOL 208location and position (x,y,z) and/or tilt or tip with respect to thedirection of the emission of radiation from the pulsed radiation system202. The sensors 210 may alternatively or additionally include one ormore of a wavefront sensor such as a Hartmann-Shack sensor, AstonHalometer, or Rostock Glare Perimeter, or other sensor(s) describedherein in accordance with certain embodiments, that sense, detect,and/or measure attributes of the eye and/or IOL (208) associated withvisual correction along the optical path of a subject's eye (e.g., eye10 in FIGS. 1A and 1B) The relay unit 206, in accordance with someembodiments, is configured to deliver the laser pulses to the IOL 208and may be configured to collect and/or direct light, for example tocollect OCT light for OCT images. The relay unit 206 may include one ormore optical elements such as focusing lens(es) or mirrors to correctlydirect the laser pulses to the intended points of the eye and/or IOL 208

Various aspects of refractive index changes required to achieve thecorrection, as sensed, detected and/or measured by the sensors 210, forexample, can be calculated by the use of a processor which may be, insome embodiments, included in the control system 204. The processor maybe the processing unit 302 shown in the computer 300 of FIG. 3. Thepulsed radiation can then be applied to the IOL at selected areas toachieve the determined correction, and the correction can subsequentlybe verified by the sensors 208.

In some embodiments, the control system 204 is configured to processsensed data from the sensors 210, such as obtained OCT data, to controla scanning mirror for directing the pulsed radiation (e.g., laserpulses) according to a particular scan pattern, across one or moreportions of the IOL 208, and can control one or more through-focusoptical elements. The control system 204, in some embodiments, isconfigured to receive one or more treatment and control parameters (e.g,from sensors 210) and to control the pulsed radiation system 202, whichcan be a pulsed laser system.

In some embodiments, the control system 204 can be configured tocalculate, based on the treatment and control parameters, a pattern oflaser pulses and/or selected areas of the IOL 208 to which the laserpulses are to be applied. The control system 204 can also be configuredto control the pulsed laser system 202 to apply the calculated patternof laser pulses to the calculated selected areas of the IOL 208 andthereby create a desired diffractive pattern in the IOL 208 (which can,in some embodiments, produce a phase shift). In some embodiments, thetreatment and control parameters correspond to conditions (e.g.,post-surgical states) and associated corrections that are needed toprovide improved vision to the subject, for example residual sphericalerror, astigmatism, and others as described with respect to the variousembodiments herein. In some embodiments, the cornea and/or anteriorchamber are taken into account for the treatment and control parameters.For example, effects of refraction at the corneal surface may be takeninto account to ensure that applied laser pulses are directed to anintended point within an IOL. In some embodiments, the treatment andcontrol parameters may include specific attributes of the eye, forexample the corneal topography.

In various embodiments described herein, optical parameters of radiationapplied to the IOL (as part of a calculated pattern, for example) caninclude, but are not limited to, the wavelength, pulse duration,frequency, energy, and/or other parameters can be specifically selectedto produce, by the refractive index writing, a desired result, where thespecific parameters depending upon the particular embodiments asdescribed herein in which various types of corrections are needed toaddress various conditions to improve the vision of the subject. Indescribing some embodiments of the present disclosure below, particularoperating parameters and other settings of a system such as the systemshown in FIG. 2 may be indicated.

Example Computing System

FIG. 3 is diagram showing a general computing system capable ofimplementing one or more embodiments of the present disclosure describedherein. Computer 300 may be configured to perform one or more functionsassociated with embodiments described herein, for example embodimentsillustrated in one or more of FIGS. 2 and/or 4-21. It should beappreciated that the computer 300 may be implemented within a singlecomputing device or a computing system formed with multiple connectedcomputing devices. For example, the computer 300 may be configured for aserver computer, desktop computer, laptop computer, or mobile computingdevice such as a smartphone or tablet computer, or the computer 300 maybe configured to perform various distributed computing tasks, which maydistribute processing and/or storage resources among the multipledevices.

As shown, the computer 300 includes a processing unit 302, a systemmemory 304, and a system bus 306 that couples the memory 304 to theprocessing unit 302. The computer 300 further includes a mass storagedevice 312 for storing program modules. The program modules 314 mayinclude modules executable to perform one or more functions associatedwith embodiments illustrated in one or more of FIGS. 2 and/or 4-21. Forexample, the program modules 314 may be executable to perform one ormore of the functions for making determinations with respect to variousoptical attributes, performing calculations, and/or executing software(e.g., computer-executable instructions stored on non-transitorycomputer-readable media) as described herein with regard to specificembodiments. The mass storage device 312 further includes a data store316.

The mass storage device 312 is connected to the processing unit 302through a mass storage controller (not shown) connected to the bus 306.The mass storage device 312 and its associated computer storage mediaprovide non-volatile storage for the computer 300. By way of example,and not limitation, computer-readable storage media (also referred toherein as “computer-readable storage medium” or “computer-storage media”or “computer-storage medium”) may include volatile and non-volatile,removable and non-removable media implemented in any method ortechnology for storage of information such as computer-storageinstructions, data structures, program modules, or other data. Forexample, computer-readable storage media includes, but is not limitedto, RAM, ROM, EPROM, EEPROM, flash memory or other solid state memorytechnology, CD-ROM, digital versatile disks (“DVD”), HD-DVD, BLU-RAY, orother optical storage, magnetic cassettes, magnetic tape, magnetic diskstorage or other magnetic storage devices, or any other medium which canbe used to store the desired information and which can be accessed bythe computer 300. Computer-readable storage media as described hereindoes not include transitory signals.

According to various embodiments, the computer 300 may operate in anetworked environment using connections to other local or remotecomputers through a network 318 via a network interface unit 310connected to the bus 306. The network interface unit 310 may facilitateconnection of the computing device inputs and outputs to one or moresuitable networks and/or connections such as a local area network (LAN),a wide area network (WAN), the Internet, a cellular network, a radiofrequency network, a Bluetooth-enabled network, a Wi-Fi enabled network,a satellite-based network, or other wired and/or wireless networks forcommunication with external devices and/or systems. The computer 300 mayalso include an input/output controller 308 for receiving and processinginput from a number of input devices. Input devices may include, but arenot limited to, sensors (e.g., sensors 210), keyboards, mice, stylus,touchscreens, microphones, audio capturing devices, or image/videocapturing devices. An end user may utilize such input devices tointeract with a user interface, for example a graphical user interface,for managing various functions performed by the computer 300.

The bus 306 may enable the processing unit 302 to read code and/or datato/from the mass storage device 312 or other computer-storage media. Thecomputer-storage media may represent apparatus in the form of storageelements that are implemented using any suitable technology, includingbut not limited to semiconductors, magnetic materials, optics, or thelike. The program modules 314 may include software instructions that,when loaded into the processing unit 302 and executed, cause thecomputer 300 to provide functions associated with embodimentsillustrated in FIGS. 2 and/or 4-21. The program modules 314 may alsoprovide various tools or techniques by which the computer 300 mayparticipate within the overall systems or operating environments usingthe components, flows, and data structures discussed throughout thisdescription. In general, the program module 314 may, when loaded intothe processing unit 302 and executed, transform the processing unit 302and the overall computer 300 from a general-purpose computing systeminto a special-purpose computing system.

As another example, the computer-storage media may be implemented usingmagnetic or optical technology. In such implementations, the programmodules 314 may transform the physical state of magnetic or opticalmedia, when the software is encoded therein. These transformations mayinclude altering the magnetic characteristics of particular locationswithin given magnetic media. These transformations may also includealtering the physical features or characteristics of particularlocations within given optical media, to change the opticalcharacteristics of those locations. Other transformations of physicalmedia are possible without departing from the scope of the presentdisclosure.

Correcting IOL Power

Some aspects of the present disclosure relate to the use of refractiveindex writing to make negative or positive power additions to animplanted IOL to correct incorrect IOL power, which may be caused bypre-surgical incorrect IOL power calculations due to, for instance,limitations in biometry accuracy. Current post-surgical refractiveconditions can include the need for both negative and positive poweradjustment. In some embodiments, through the use of RIW to impose aphase pattern with a total phase addition of up to one lambda, with zonewidth calculated to achieve appropriate power change and the correctslope, both negative and positive additions can be made. Furthermore,alternative embodiments can include phase patterns with step heightlarger than one lambda which can achieve the desired monofocal shift.

The process to adjust the power can be planned in advance. While addingpositive diffractive power can reduce longitudinal chromatic aberrations(thereby increasing image quality), adding negative diffractive powercan increase it. In accordance with certain embodiments, a postsurgicalrefractive index writing procedure is planned in the protocol, andtherefore the power calculation for an IOL to be implanted in a subjectcan be intentionally set to leave the subject with a spherical errorrequiring an estimated positive addition. For example, IOL power can becalculated to leave a subject with a spherical error of +1.5 D; with therange of expected spherical variation being 1.5 D, corrections can bemade to improve a longitudinal chromatic aberration, and therefore,image quality.

Spherical aberration (spherical error) of the added power can becontrolled. While a default correction mode of solely adding powerinduces spherical aberration (the magnitude and sign of which depends onthe spherical aberration that needs to be corrected), the correctionfactor, in accordance with some embodiments, does not alter the overallspherical aberration; this can be achieved by having the size of eachzone in r²-space be non-uniform rather than fixed if the change in poweris achieved with a diffractive phase pattern. Alternatively, sphericalaberration can be combined with the spherical correction to modulate therefractive index change required along the r-space to create arefractive change in power. In some embodiments, some residual sphericalaberration is left uncorrected, for example in cases where an extendeddepth of focus is desired.

In some aspects of the present disclosure, according to one embodiment,an IOL is implanted in the eye of a subject, where the IOL is configured(pre-surgery) to, when implanted, leave a non-zero residual sphericalerror that requires an estimated diffractive power addition in the IOL.The IOL selected may be an IOL selected that would result in aparticular average error, e.g., +2.5 diopters, according to, forinstance, the Haigis formula. Furthermore, the estimation-calculation ofthe needed positive power addition can be performed based on severalfactors that are specific to a particular subject. For example, thecalculations can be performed based on one or more of: estimated IOLpower to target refraction, subject axial length, surgeon's optimized Aconstant or surgical factor, and/or effective lens position (ELP). The“A constant” refers to a personalized regression factor that accountsfor individual differences in technique, and “axial length” refers tothe distance between apex and the cornea and the retina.

Regarding the refractive index writing, in some embodiments, a pluralityof laser pulses are applied to selected area(s) of the implanted IOL,where the laser pulses are applied according to a predetermined patternconfigured to produce, by the MW, a positive diffractive power additionin the IOL that corrects for the residual spherical error and partiallyreduces or completely compensates for a longitudinal chromaticaberration of the eye. The applied laser pulses produce the positivediffractive power addition in the IOL in order to partially or fullycorrect for the longitudinal spherical chromatic aberration.

In some embodiments, the power addition does not induce furtherspherical aberration or modify existing spherical aberration. In otherembodiments, a spherical aberration change is induced by the RIW tochange the size of diffractive profile zone(s) of the IOL in r²-space,such that there is non-uniform size of each zone in r²-space. In orderto reduce spherical aberration there is higher spacing as high r² valuesare approached, and in order to increase spherical aberration, there islower spacing towards the high r² values.

In some embodiments, to compensate for the residual error(s) in theimplanted IOL, a phase profile induced on the IOL by RIW is calculatedbased at least on the effective lens position (ELP). To create theprofile, the postoperative refractive error in the spectacle plane needsto be converted to power shift on the IOL plane. In some embodiments,ELP measured during the refractive index writing procedure is utilizedto calculate the correct conversion between spherical equivalent (SEQ)in the spectacle plane and power shift in the IOL plane for eachindividual subject using an average corneal eye or the subject's cornealpower. The conversion can be implemented depending on the different eyemodels proposed. Refractive error is measured as, e.g., the optimaltrial lenses to place outside the subject's eye to achieve emmetropia.In some embodiments, the RIW treatment can be personalized to accountfor ELP, rather than every subject receiving the same RIW treatmentbased on the size of the refractive error in diopters. Thepersonalization can be calculated by various ways through implementingdifferent IOL models, but have in common that they constitute arefractive calculation utilizing geometric optics or ray tracingsimulation to achieve optimal focus on the retina.

As table 1 (below) shows for an average eye, considering the ELP in thecalculations with calculations of the estimated-desired power correctionto be made in the IOL can significantly impact the outcomes.

TABLE 1 Post-operative SEQ Power shift in the IOL plane (D) in spectacleplane (D) ELP = 4.5 mm ELP = 4.7 mm −2 −2.72 −2.45 −1.5 −2.02 −1.74 −0.5−0.68 −0.35 0.5 0.64 1.00 1.5 1.97 1.67 2 2.61 3.01

One aspect of the present disclosure relates to a method for improvingvision of a subject implanted with an intraocular lens (IOL) having anon-zero residual spherical error that requires an estimated diffractivepower addition in the IOL. In one embodiment, the method can includeapplying a plurality of laser pulses to the IOL. The laser pulses can beconfigured to produce, by refractive index writing on the IOL, theestimated diffractive power addition to correct for the residualspherical error.

In some embodiments, the power addition can be a positive diffractivepower addition that at least partially reduces a longitudinal chromaticaberration of the eye. Applying the plurality of laser pulses caninclude applying a plurality of focused laser pulses according to apredetermined pattern to at least one selected area of the IOL, toproduce the diffractive power addition. In some embodiments, theestimated diffractive power addition fully compensates for thelongitudinal chromatic aberration. The diffractive power addition can beestimated based at least in part on at least one of: estimated IOL powerto target emmetropia; a subject's axial length; surgeon's optimized Aconstant; and/or effective lens position (ELP). In some embodiments, thelaser pulses are configured and applied to the IOL such that the poweraddition does not induce further spherical aberration or modify existingspherical aberration.

In some embodiments, control of the spherical aberration is performed atleast in part by changing the phase profile of the IOL by refractiveindex writing. In some embodiments, control of the spherical aberrationcan be performed at least in part by changing, by the refractive indexwriting on the IOL, the size of diffractive profile zones in r² space.In some embodiments, a phase profile induced in the IOL to correct forresidual errors is calculated based at least in part on effective lensposition (ELP) measured during the refractive index writing.

According to another aspect, the present disclosure relates to a methodfor improving vision of a subject implanted with an IOL that has anon-zero residual spherical error. In one embodiment, the methodincludes applying a plurality of laser pulses to the IOL. The laserpulses can be configured to produce, by refractive index writing on theIOL, an estimated positive diffractive power addition. A phase profileinduced in the IOL to correct for residual errors can be calculatedbased at least in part on effective lens position (ELP) measured duringthe refractive index writing. In some embodiments, applying theplurality of laser pulses comprises applying a plurality of focusedlaser pulses to at least one selected area of the IOL to produce, by therefractive index writing on the IOL, the diffractive power addition inthe IOL.

In some embodiments, the diffractive power addition at least partiallycorrects a longitudinal chromatic aberration of the eye. The diffractivepower addition can be estimated based at least in part on at least oneof: estimated IOL power to target emmetropia; a subject's axial length;and surgeon's optimized A constant. In some embodiments, the laserpulses are configured and applied to the IOL such that the poweraddition does not induce further spherical aberration or modify existingspherical aberration. Control of the spherical aberration can beperformed at least in part by changing, by the refractive index writingon the IOL, the size of diffractive profile zones in r² space.

In another aspect, the present disclosure relates to a system forimproving vision of a subject. In one embodiment, the system includes apulsed laser system configured to apply laser pulses to an intraocularlens (IOL) implanted in an eye of a subject to change the refractiveindex of selected areas of the lens by refractive index writing. Thesystem can also include a control system configured to receive dataregarding a non-zero residual spherical error of the eye of the subjectafter implantation of the IOL and estimate a diffractive power additionto the IOL required to either partially or fully correct the non-zeroresidual spherical error. The control system can be coupled to thepulsed laser system and configured to control the pulsed laser system toapply a plurality of laser pulses to the IOL. The laser pulses can beconfigured to produce, by refractive index writing on the IOL, theestimated diffractive power addition.

In some embodiments, the control system is configured to estimate thediffractive power addition such that the diffractive power additionreduces a longitudinal chromatic aberration of the eye. In someembodiments, the pulsed laser system is configured to apply a pluralityof focused laser pulses to at least one selected area of the IOL toproduce, by the refractive index writing on the IOL, the estimateddiffractive power addition in the IOL. The estimated diffractive poweraddition can fully compensate for the longitudinal chromatic aberrationof the eye. In some embodiments, the diffractive power addition can beestimated based at least in part on IOL power to achieve emmetropia. Insome embodiments, the diffractive power addition is estimated based atleast in part on the axial length of the subject's eye. In someembodiments, the diffractive power addition is estimated based at leastin part on the effective lens position (ELP) of the IOL in the subject'seye.

In some embodiments, the control system is configured to control thepulsed laser system to apply the plurality of laser pulses to the IOLsuch that the power addition does not induce further sphericalaberration or modify existing spherical aberration of the IOL. In someembodiments, at least the control system is configured to control thepulsed laser system to control spherical aberration at least in part bychanging, by the refractive index writing on the IOL, the size ofdiffractive profile zones in r² space. The control system can beconfigured to estimate, based at least in part on effective lensposition (ELP) measured during the refractive index writing, the phaseprofile induced in the IOL. In some embodiments, the system can alsoinclude a sensor to measure the non-zero residual spherical error of theeye of the subject and transmit sensed data associated with the non-zeroresidual spherical error to the control system.

Correcting Astigmatism

Uncorrected astigmatism results in impaired contrast sensitivity andvisual acuity, which has safety implications for subjects. Although atoric IOL can be implanted to correct for corneal astigmatism, residualastigmatism is common after cataract surgery due to different factorslike surgically induced astigmatism, effect of posterior cornealastigmatism, incorrect toric IOL power determination, toric IOL rotationor misplacement, and/or use of non-toric IOLs in toric corneas. Aconventional procedure to calculate the zone radii of full lambda phaseshift to correct for a spherical error F is to use the formula:

$r = \sqrt{m\frac{2\lambda}{F}}$

where λ is the wavelength, m is a natural number (1, 2, 3, . . . ) and Fthe power.

In accordance with some embodiments of the present disclosure, the phaseprofile induction is modified to include an angular dependence; in someembodiments, the following calculation is utilized:

$r = \sqrt{m\frac{2\lambda}{F_{1} + {\left( {F_{2} - F_{1}} \right){{\sin \; \theta}}}}}$

where θ is the angle, and F1 and F2 the power to be corrected in therespective meridians. This can be used to correct the astigmatism of thesubject.

In some embodiments of the present disclosure, a method for improvingvision of a subject having an implanted intraocular lens (IOL) includesthe steps of: determined a modification of a phase profile on the IOL tocorrect an astigmatism; and applying a plurality of focused laser pulsesto one or more selected areas of the IOL, where the laser pulses areconfigured to produce, by refractive index writing on the IOL, thedetermined modification of the phase profile on the IOL. Determining themodification of the phase profile includes calculating a radius of aphase shift for correcting for a residual spherical error, the radiusbeing calculated according to factors that include an angulardependence. The radius of the phase shift can be calculated by theabove-described equation (1) above.

Spectacle Independence

Spectacle dependence can be due to monofocal IOL implantation, forexample, or incorrect selection of a suitable presbyopia-correcting IOLfor a particular subject. Presbyopia-correcting intraocular lenses (PCIOLs) that make subjects spectacle independent can be highly desired.While spectacle independence is the expected result of cataract surgerywith certain presbyopia-correcting IOLs, some subjects receiving thoseIOLs may still need to wear spectacles (i.e., they are still spectacledependent) for the above-stated or other reasons. Parameters related tospectacle dependence include through-focus visual acuity of the subject,comfortable reading distance of the subject, subject biometry (such asat least one of axial length of the subject's eye IOL position, andcorneal power), subject-specific reading habits (including readingdistances), pupil size and subject-specific data indicating commonlifestyle tasks performed by the subject and/or lighting conditionsassociated with respective tasks.

In accordance with some embodiments of the present disclosure, subjectswho have previously had monofocal IOLs surgically implanted can benefitfrom a refractive index writing (MW) that produces phase profilessimilar to those in presbyopia-correcting IOLs, for example phaseprofiles shown and described in one or more of the following publishedpatent applications, which are incorporated herein by reference: U.S.Patent Application Publication Nos. 2018-0368972; 2019/0004335;2019/0000433; 2019/0004221. Certain embodiments provide for the specificapplication of many desired phase profiles in-vivo. Further, accordingto some embodiments, RIW can be used to convert a particular PC IOLtreatment into another that may be more suitable for the subject. Forexample, if the subject gets an extended depth of focus IOL but aftersurgery is not satisfied with near vision, refractive index writing canbe used to write another design that better suits the subject'sspectacle independence needs. Alternatively, if the subject is notsatisfied by the distance image quality or the intermediate performanceprovided by a particular design aimed to provide a higher degree ofspectacle independence, refractive index writing can be used to writeanother design with a greater quality of vision or better intermediatevision.

There is an important relationship between through focus visual acuity(VA) and rates of spectacle independence. While IOLs have an expectedaverage through focus VA curve, which is related to expected rates ofspectacle independence, individual through focus VA curves can radicallydiffer from the expected curves, and as a result, individual subjectsmight need to wear spectacles. For instance, an individual subject mighthave a lower than expected VA at 30 cm, 40 cm, or 50 cm. In accordancewith some embodiments of the present disclosure, a particular subject'sthrough focus VA curve is measured, and the results are combined with analgorithm to predict spectacle independence from through focus VA. Amultifocal addition produced by refractive index writing can beimplemented to produce a certain phase change in the IOL which mostoptimally benefits spectacle independence for a particular subject'sneeds, for example improved VA at 30 cm, 40 cm, or 50 cm.

Improving spectacle independence may include improving the subject'sthrough-focus visual acuity at one or more first distances (optionallywhile maintaining the subject's through-focus visual acuity at one ormore second distances), extending depth of focus of the IOL, providingthe IOL with at least partial presbyopia correction, improvingpresbyopia correction of the IOL and adapting presbyopia correction ofthe IOL to subject-specific requirements such as subject biometry orsubject-specific lifestyle data.

Predicting the spectacle independence can, in some embodiments, utilizea Bayesian analysis method, involving calculating the probability ofachieving spectacle independence for at least two IOLs based on at leastone of: clinical data providing visual acuity at a second defocusposition for the at least two IOLs in the population; standard deviationof pre-clinical visual acuity for the at least two IOLs at the first orthe second defocus positions; clinical data providing minimum readableprint size in mm in the population; modulation transfer function (MTF)at one or more frequencies at different distances for different pupilsizes; and/or area under the modulation transfer function at one or morefrequencies at different distances for different pupil sizes.

The Bayesian analysis method can be expanded to incorporate othercharacteristics of the subjects, such as age, gender, eye length, pupilsize, ethnicity, corneal aberrations, life style or combinationsthereof. The Bayesian analysis method of estimating spectacleindependence for different parameters can be incorporated in an IOLdesign and/or manufacturing process. The parameter space of IOL designallows variation of IOL characteristics such as radii of curvature,diffraction power, diffraction step height, transition zones and IOLthickness. These characteristics can be used in a ray tracing simulationsoftware to predict through focus MTF, which can predict VA. UsingBayesian analysis, the probability of spectacle independence can becalculated, and the IOL characteristics optimized such that the highestpossible spectacle independence is achieved, in conjunction with othersimulated and desired constraints such as distance image quality.Bayesian analysis can also be used to predict how suitable certaintreatment techniques, such as making the subjects slightly myopicpostoperatively can positively affect spectacle independence. Bayesiananalysis to estimate spectacle independence can also be used to selectan IOL for implantation in a subject that would increase the chance ofthe subject to be spectacle independent for a variety of tasks such asreading, viewing a smartphone, computer use or combinations thereof.

In some embodiments, diagnostics combined with customization of IOLsusing RIW can provide customized results that take into accountsubject-specific individualized factors including one or more of: thesubject's common reading behavior, for example his/her preferred readingdistance; pupil size considerations along with the lighting conditionspresent during common tasks the subject performs in daily life; and/oraberrations of both eyes of the subject, for optimizing binocular visionby matching the aberrations in order to result in optimal (e.g.,highest) depth perception.

In one aspect, the present disclosure relates to a method for improvingvision of a subject having an implanted intraocular lens (IOL). In oneembodiment, the method includes applying a plurality of laser pulses tothe IOL. The laser pulses can be configured to produce, by refractiveindex writing on the IOL, a predetermined change in phase profile of theIOL to increase spectacle independence. In some embodiments, applyingthe plurality of laser pulses includes applying a plurality of focusedlaser pulses according to a predetermined pattern to at least oneselected area of the IOL to produce the predetermined change in phaseprofile.

In some embodiments, the predetermined change in phase profile toimprove spectacle independence can be determined by performing functionsthat include, prior to the application of the laser pulses to the IOL,acquiring measurements that include measurements associated withsubject-specific through-focus visual acuity. The functions performedcan also include predicting based at least in part on the acquiredmeasurements, an estimated phase profile for increasing near vision forthe subject while maintaining distance vision, or for the increasing ofdistance vision for the subject while maintaining near vision andintermediate vision. In some embodiments, the phase delay is estimatedbased at least in part on measurements associated with subject-specificthrough-focus visual acuity. In some embodiments, the IOL is amultifocal IOL and the refractive index writing produces a phase profileon the IOL that changes the add power of the multifocal IOL.

In some embodiments, the change of the add power produced by therefractive index writing phase profile is calculated based on at leastone of: through focus visual acuity of the subject; comfortable readingdistance of the subject; and/or subject biometry. The subject biometrycan include at least one of axial length of the subject's eye, IOLposition, and/or corneal power.

In some embodiments, the predetermined change in phase profile isdetermined, prior to the application of the laser pulses to the IOL,based at least in part on: subject-specific reading habits, includingreading distances; pupil size; and/or subject-specific data indicatingcommon lifestyle tasks performed by the subject and lighting conditionsassociated with respective tasks. In some embodiments, the IOL is adiffractive IOL or a multifocal refractive IOL. In some embodiments, thechange in phase profile is estimated by calculating the phase differencebetween the existing phase profile of the implanted IOL and the desiredphase profile expected after the refractive index writing.

In another aspect, the present disclosure relates to a method forimproving vision of a subject having an implanted intraocular lens. Inone embodiment, the method can include applying a plurality of laserpulses to the IOL; the laser pulses can be configured to produce, byrefractive index writing on the IOL, a predetermined change in phaseprofile of the IOL to increase spectacle independence. The predeterminedchange in phase profile can be determined at least in part onmeasurements associated with subject-specific through-focus visualacuity. The measurements can be acquired prior to the application of thelaser pulses to the IOL. Applying the plurality of laser pulses caninclude applying a plurality of focused laser pulses according to apredetermined pattern to at least one selected area of the IOL toproduce the predetermined change in phase profile.

In some embodiments, the predetermined change in phase profile toimprove spectacle independence can be determined by performing functionsthat include predicting, based at least in part on the acquiredmeasurements, an estimated phase profile for increasing near vision forthe subject while maintaining distance vision, or the increasing ofdistance vision for the subject while maintaining near vision.

In some embodiments, the predetermined change in phase profile toimprove spectacle independence can be determined by performing functionsthat include predicting, based at least in part on the acquiredmeasurements, an estimated phase profile for increasing intermediatevision for the subject while maintaining distance vision, or theincreasing of distance vision for the subject while maintainingintermediate vision.

In some embodiments, the predetermined change in phase profile toimprove spectacle independence can be determined by performing functionsthat include predicting, based at least in part on the acquiredmeasurements, an estimated phase profile for increasing intermediatevision for the patient while maintaining near vision, or the increasingof near vision for the patient while maintaining intermediate vision.

In some embodiments, the phase delay can be estimated based at least inpart on measurements associated with subject-specific through-focusvisual acuity. In some embodiments, the IOL can be a multifocal IOL andthe refractive index writing produces a phase profile to change the addpower of the multifocal IOL. In some embodiments, the change of the addpower produced by the refractive index writing of the phase profile canbe calculated based on: through-focus visual acuity of the subject;comfortable reading distance of the subject; and/or subject biometry.The subject biometry can include axial length, IOL position, and/orcorneal power.

In some embodiments, the predetermined change in phase profile isdetermined, prior to the application of the laser pulses to the IOL,based at least in part on: subject-specific reading habits, including:reading distances; pupil size; and/or subject-specific data indicatingcommon lifestyle tasks performed by the subject and lighting conditionsassociated with respective tasks.

In some embodiments, the IOL can be a diffractive IOL or a multifocalrefractive IOL. In some embodiments, the change in phase profile isestimated by calculating the phase difference between the existing phaseprofile of the implanted IOL and the desired phase profile expectedafter the refractive index writing.

In another aspect, the present disclosure relates to a system forimproving vision of a subject. In one embodiment, the system includes apulsed laser system configured to apply a plurality of laser pulses toselected areas of an intraocular lens (IOL) implanted in an eye of asubject to change the refractive index of the selected areas byrefractive index writing. The system can also include a control systemconfigured to receive parameters related to spectacle dependence of theeye of the subject after implementation of the IOL and to calculate,based on the parameters, a pattern of laser pulses and selected areas ofthe intraocular lens to which the laser pulses are to be applied toprovide a change in phase profile of the IOL to increase spectacleindependence. The control system can be coupled to the pulsed lasersystem and configured to control the pulsed laser system to apply thecalculated pattern of laser pulses to the calculated selected areas ofthe intraocular lens.

In some embodiments, the parameters related to spectacle dependence caninclude measurements associated with subject-specific through-focusvisual acuity. In some embodiments, the control system can be configuredto determine the change in phase profile. In some embodiments,determining the change in phase profile can include predicting, based atleast in part on the subject-specific through-focus visual acuitymeasurements, an estimated phase profile for increasing near vision forthe subject while maintaining distance vision, or for increasingdistance vision for the subject while maintaining near vision.

In some embodiments, the parameters related to spectacle dependenceinclude measurements associated with subject-specific through-focusvisual acuity, wherein the control system is configured to determine thechange in phase profile. Determining the change in phase profile caninclude predicting, based at least in part on the subject-specificthrough-focus visual acuity measurements, an estimated phase profile forincreasing intermediate vision for the subject while maintainingdistance vision, or increasing distance vision for the subject whilemaintaining intermediate vision.

In some embodiments, the parameters related to spectacle dependenceinclude measurements associated with subject-specific through-focusvisual acuity, wherein the control system is configured to determine thechange in phase profile, and wherein determining the change in phaseprofile can include: predicting, based at least in part on thesubject-specific through-focus visual acuity measurements, an estimatedphase profile for increasing intermediate vision for the subject whilemaintaining near vision, or for increasing near vision for the subjectwhile maintaining intermediate vision. In some embodiments, the controlsystem can be configured to estimate phase delay based at least in parton measurements associated with subject-specific through-focus visualacuity. In some embodiments, the IOL can be a multifocal IOL and therefractive index writing can produce a phase profile on the IOL thatchanges the add power of the multifocal IOL.

In some embodiments, the control system can be configured to calculatethe change of the add power produced by the refractive index writingphase profile based on at least one of: through-focus visual acuity ofthe subject; comfortable reading distance of the subject; and/or subjectbiometry. In some embodiments, the subject biometry can include axiallength of the subject's eye, IOL position, and/or corneal power.

In some embodiments, the control system can be configured to determinethe change in phase profile, prior to the application of the laserpulses to the IOL, based at least in part on: subject-specific readinghabits, including reading distances; pupil size; and/or subject-specificdata indicating common lifestyle tasks performed by the subject and/orlighting conditions associated with respective tasks. In someembodiments, the parameters related to spectacle dependence include:through-focus visual acuity of the subject; comfortable reading distanceof the subject; subject biometry, such as at least one of axial lengthof the subject's eye, IOL position, and/or corneal power;subject-specific reading habits, including reading distances; pupilsize; and/or subject-specific data indicating common lifestyle tasksperformed by the subject and/or lighting conditions associated withrespective tasks. In some embodiments, the IOL can be a diffractive IOLor a multifocal refractive IOL.

In some embodiments, the change in phase profile can be estimated bycalculating a phase difference between an existing phase profile of theimplanted IOL and a desired phase profile expected after the refractiveindex writing. In some embodiments, improving spectacle independenceincludes one or more of: improving the subject's through-focus visualacuity at one or more distances; improving the subject's through-focusvisual acuity at one or more first distances while maintaining thesubject's through-focus visual acuity at one or more second distances;extending depth of focus of the IOL; providing the IOL with at leastpartial presbyopia correction; improving presbyopia correction of theIOL; and adapting presbyopia correction of the IOL to subject-specificrequirements, such as subject biometry or subject-specific lifestyledata.

Photic Phenomenon

Unwanted visual symptoms due to the presence of unwanted light forsubjects, also referred to herein as “photic phenomenon” include but arenot limited to: halos, starbursts, and glare. Such unwanted visualsymptoms tend to be more commonly experienced in subjects after thesurgical implantation of a presbyopia-correcting intraocular lenses. Formultifocal IOLs, the out of focus light can form a halo around the mainimage. The presence of unwanted visual symptoms strongly depends on thespecific IOL design, but there is also a significant subjectivecomponent. For that reason, for two subjects with similar objectiveocular conditions, one may not experience unwanted visual symptoms whilethe other may experience them and express complaints about thecondition. Although medical professionals can make great efforts toselect monofocal refractive IOLs for subjects with a high risk ofexperiencing unwanted post-surgical visual symptoms, such symptoms canbe difficult to predict, particularly on a subject-by-subject basis.

As mentioned above, while medical professionals can go to great lengthto ensure subject expectations are managed prior to IOL implantationsurgery, some subjects nevertheless realize after surgery that theywould have preferred a monofocal IOLs or a lens that would provide alower degree of photic phenomena. Rather than requiring the IOL to besurgically replaced, which can be a complicated and risky procedure, inaccordance with some embodiments of the present disclosure refractiveindex writing is used to remove or substitute the optical design causingthe unwanted visual symptoms. As shown in FIG. 4, according to oneexample implementation, the diffractive profile 402 introduces aradially dependent phase shift; this phase shift also creates unwantedvisual symptoms. According to some embodiments, a radially dependentphase shift 404 is introduced to compensate, such that the IOL can berendered monofocal, removing the unwanted visual symptoms. That is, inFIG. 4, the portion 402 illustrates phase addition of apresbyopia-correcting IOL, and the portion 404 illustrates the phaseaddition needed to be introduced, by refractive index writing, to removethe unwanted visual symptoms. In some embodiments of the presenteddisclosure, the phase delay introduced by a diffractive IOL is fullycompensated. In other embodiments of the present disclosure, a partialcompensation of the profile may be performed, or the creation of anotherprofile that is expected to create less visual disturbances for aparticular subject and therefore a better quality of vision.

In some embodiments as discussed above, a phase-compensation techniqueby RIW is used to eliminate all visual symptoms of a diffractive andrefractive IOL, by fully compensating the added phase. This can alsoeliminate the spectacle independence created by the IOL, however. Inaccordance with some embodiments, a subject-specific, personalizedapproach is taken that can enable certain subjects to receive adesirable compromise of reduced unwanted visual symptoms and maintainedspectacle independence. In accordance with some embodiments of thepresent disclosure described below, this compromise-type approach caninclude: 1. a personalized diagnostic procedure mapping when intolerablelevels of visual symptoms occur; 2. a personalized correction involvingrefractive optimization, apodization, and/or profile reversion; and 3. adiagnostic procedure verifying satisfactory reduction of unwanted visualsymptoms.

In some embodiments, the use of such approaches can be combined withsimulated optical manipulations, including modulating the pupil size,and higher order aberrations. Certain pupil sizes and higher orderaberrations interact with the diffractive design to exacerbate thevisual symptoms, and this step would measure this on a personalizedlevel.

With respect to the above-mentioned personalized diagnostic proceduremapping when intolerable levels of visual symptoms occur, fullysubjective, psychophysical, and/or objective approaches can be used formeasuring and mapping unwanted visual symptoms, including halos, glareand starbursts. These may include one or more aspects and embodimentsshown and described in U.S. patent application Ser. No. 16/271,648,entitled “Psychophysical Method to Characterize Visual Symptoms”, filedFeb. 8, 2019, which is hereby incorporated by reference. Fullysubjective approaches include, for example, the use of questionnaires tosolicit feedback from a particular subject in order to receive, forinstance, descriptions and/or drawings that articulate the photicphenomena he/she is experiencing. Psychophysical approaches include, forexample, use of commercially available devices such as an AstonHalometer and/or a Rostock Glare Perimeter, which can quantify halos.Objective approaches can include wavefront-based methods, such as theObjective Scatter Index.

With respect to the above-mentioned personalized correction involvingrefractive optimization, apodization, and/or profile reversion,refractive optimization includes correcting one or more of defocus,astigmatism, and higher order aberrations. Regarding apodization, theperipheral part of the diffractive design, e.g., 4 mm and higherdiameter, or 3 mm and higher diameter, can be eliminated, while thecentral part can be kept; additionally, multifocality can be modified inthe peripheral part of the IOL to allow a different light distributionbetween the different foci, for example, to increase the amount of lightthat goes to the far focus and therefore, reducing the amount of lightthat goes to the near and/or focus. The diameter can be chosen based onindividual results. In profile reversion, the full multifocal profile ofthe IOL is eliminated and a monofocal profile created.

With respect to the above-mentioned verification of satisfactoryreduction of unwanted visual symptoms for the subject, through adiagnostic procedure, refractive optimization, apodization, and/orprofile reversion can be done independently or sequentially to eliminateunwanted visual symptoms. Additionally, apodization can be performedusing subject feedback by eliminating multifocality in the outer partsof the IOL and, if more reduction is desired, a further elimination ofmultifocality to a lower radius.

In some embodiments, refractive index writing is implemented to providea phase addition that simulations show would decrease the unwantedvisual phenomenon. For example, if a subject complains about haloeffects, then the added phase is configured such that it results insmaller magnitude of light outside the focus according to simulations.As another example, if a subject complained about experiencing rings andspiderwebs, then the simulation should result in lower variance insimulated light levels (light intensity going up and down as a functionof radius). According to some embodiments, this can be particularlyuseful to simulate on an individual basis to include the interactioneffect between higher order aberrations and unwanted visual symptoms.

In one aspect, the present disclosure relates to a method for improvingvision of a subject having an implanted intraocular lens (IOL). In oneembodiment, the method includes determining at least one photicphenomenon experienced by the subject after implantation of the IOL; andapplying a plurality of laser pulses to the IOL. The laser pulses can beconfigured to produce, by refractive index writing on the IOL, a phaseshift in the IOL to compensate for the photic phenomenon.

In some embodiments, applying the plurality of laser pulses includesapplying a plurality of focused laser pulses, according to apredetermined pattern, to at least one selected area of the IOL toproduce, by the refractive index writing on the IOL, the phase shift.The photic phenomenon can include a halo, starburst, and/or glare. Insome embodiments, the phase shift can include a radially dependent phaseshift. In some embodiments, the method can include verifying correctionof the at least one photic phenomenon following the application of thelaser pulses. Verifying the correction can be performed by incorporatingsubject feedback provided following the application of the laser pulses.

In some embodiments, the IOL is a diffractive IOL or a refractive IOLand compensating for the photic phenomena includes at least partiallycompensating for the phase delay. In some embodiments, determining thephotic phenomena can include measuring and mapping the photic phenomenonexperienced by the subject. Determining the phase delay to compensatefor at least one photic phenomena can include simulations of the optimalhigher order aberrations induction based on pupil size analysis. Thesimulations of the optimal higher order aberrations induction can bebased on subject response to photic phenomena.

In some embodiments, compensating for the photic phenomenon includesrefractive optimization, apodization, partial apodization, and/orprofile reversion. The refractive optimization can include correcting,by the refractive index writing, at least one of defocus, astigmatism,and higher order aberrations. The apodization can include eliminating,by inverted phase delay, the diffractive or refractive IOL design in anouter part of the lens. The apodization phase delay can be determinedusing feedback from the subject relating to experiencing the photicphenomena. The apodization can include maintaining a central part of thediffractive design, where the peripheral part is defined based on thespecific photic phenomenon experienced by the subject.

In some embodiments, the partial apodization includes modifying thepercentage of light distributed between different foci of a multifocalIOL in an outer part of the lens. The profile reversion can includeeliminating the full diffractive profile of the IOL.

As an example, an adaptive optics (AO) system can be used to evaluatethe level of higher-order aberrations that are needed to correct for thephotic phenomenon, controlling the pupil size. The measurement ofindividual aberrations can be performed using, for example, wavefrontsensors such as Hartmann-Shack sensors, and specialized software may beutilized to calculate an optimal phase map for the refractive indexwriting. In some embodiments, the simulations of the optimal higherorder aberrations induction are based on subject response to photicphenomena.

In some embodiments, correcting the higher order aberrations tocompensate for the photic phenomenon can include performing aniterative, closed-loop correction process to correct one or more of thehigher order aberrations of the subject. In some embodiments, theclosed-loop correction process includes measuring the higher orderaberrations associated with the vision of the subject and determining,based at least in part on the measurements, a target higher orderaberration correction that can be at least one of: full correction of atleast one of the higher order aberrations of the subject; partialcorrection of at least one of the higher order aberration of thesubject; and induction of at least one higher order aberration. Themethod can also include applying a plurality of focused laser pulses toselected areas of the IOL, where the laser pulses are configured toproduce, through refractive index writing, a target higher orderaberration correction profile on the IOL.

In some embodiments, the above-described closed-loop method alsoincludes the steps of determining if the produced correcting profilemeets the determined profile and, responsive to determining that theproduced correcting profile does not meet the determined profile:measuring the difference between the higher order aberrations profile ofthe eye after the laser treatment and the target higher orderaberrations correction and using this information to calculate thedetermined profile to achieve the target higher order aberrationcorrection, and, based at least in part on the measured difference,applying a plurality of focused laser pulses to the IOL for refractiveindex writing, where the configuration of the laser pulses are modifiedfrom the prior applied laser pulses based on the measured difference,and repeating the above steps until the produced higher order aberrationcorrecting profile meets the determined target higher order aberrationcorrection.

In another aspect, the present disclosure relates to a system forimproving vision of a subject. In one embodiment, the system includes apulsed laser system configured to apply laser pulses to an intraocularlens (IOL) implanted in an eye of a subject to change the refractiveindex of selected areas of the lens by refractive index writing. Thesystem can also include a control system configured to receive dataregarding a photic phenomenon of the eye of the subject afterimplantation of the IOL and use the received data to calculate a patternof laser pulses and/or selected areas of the IOL to which the laserpulses are to be applied to produce a phase shift to compensate for thephotic phenomenon. The control system can be coupled to the pulsed lasersystem and configured to control the pulsed laser system to apply thecalculated pattern of laser pulses to the calculated selected areas ofthe IOL in order to produce, by refractive index writing on the IOL, thephase shift to compensate for the photic phenomenon. In someembodiments, the photic phenomenon can include a halo, starburst, and/orglare.

In some embodiments, the control system can be configured to calculatethe pattern of laser pulses and the selected areas of the IOL to producea radially dependent phase shift. In some embodiments, the controlsystem can be configured to calculate the pattern of laser pulses andthe selected areas of the IOL to at least partially compensate for thephase delay of a diffractive IOL or a refractive IOL.

In some embodiments, the system can also include at least one sensorcoupled to the control system. The at least one sensor can be configuredto collect data regarding the pupil size of the subject and transmit thedata regarding pupil size to the control system. The control system canbe configured to compensate for the phase delay by using the dataregarding pupil size to run simulations of optimal higher orderaberrations to induce in the IOL to compensate for the photicphenomenon; and the control system can be configured to calculate thepattern of laser pulses and the selected areas of the IOL to induce theoptimal higher order aberrations. In some embodiments, the simulationsof the optimal higher order aberrations induced are based on subjectresponse to photic phenomena.

In some embodiments, compensating for the photic phenomenon can include:refractive optimization, apodization, partial apodization, and/orprofile reversion. In some embodiments, the refractive optimizationincludes correcting, by the refractive index writing, at least one ofdefocus, astigmatism, and higher order aberrations.

In some embodiments, the apodization can include eliminating, byinverted phase delay, the diffractive or refractive IOL design in anouter part of the lens. In some embodiments, the apodization can alsoinclude maintaining a central part of the diffractive design, whereinthe peripheral part is defined based on the specific photic phenomenonexperienced by the subject.

In some embodiments, the partial apodization can include modifying thepercentage of light distributed between different foci of a multifocalIOL in an outer part of the lens. In some embodiments, the profilereversion can include eliminating the full diffractive profile of theIOL.

In some embodiments, the system can include at least one sensor coupledto the control system to measure higher order aberrations, andcompensating for the photic phenomenon can include correcting the higherorder aberrations. The control system can be configured to perform aniterative, closed-loop correction process to correct the higher orderaberrations.

Negative Dysphotopsia

Negative dysphotopsia (ND) can be characterized by subjective reportsand complaints from subjects having an intraocular lens (IOL) implanted,where the complaints describe the presence of a dark shadow in the farperiphery. A number of subject factors, including small photopic pupil,high angle kappa and hyperopia, have been identified as increasing therisk of ND. The presence of ND is likely caused by absence of light inthe retinal interval between light passing through and refracted by theIOL (e.g., at lower angles of incidence) and rays missing the IOL (e.g.,at higher angles of incidence). While the light passing the IOL at thelower angles of incidence is refracted, changing its direction to alower angle, the light at the higher angles miss the IOL and continuestraight without deviation, thereby creating an angular interval on theretina that is not illuminated. The problem is partially alleviated atlarger pupil sizes, since optical errors create larger deviations ofrays at the pupil edge which partially hits the obscured part of theperipheral retina.

As described above, negative dysphotopsia can result if there is adiscontinuity in ray deviation between rays missing the IOL and raysbeing refracted by the IOL. In order to address this condition, inaccordance with some embodiments of the present disclosure, a gradualouter phase prism is applied in the outermost part of the IOL (e.g., 0.5mm from the edge of optic body) using refractive index writing procedurein subjects that complain of ND after IOL implantation. The result canbe to gradually deviate the chief ray, bridging the gap between raysmissing and rays being refracted by the IOL, eliminating or reducing theshadow. The phase prism can be defined based on the power of the IOL(e.g., from 5.0 to 34.0 D) and the extension of the prism (from the edgeto the center of the IOL). The procedure can be independent of the IOLdesign (refractive or diffractive) and the IOL platform.

Consistent with one or more aspects described above, and in accordancewith some embodiments of the present disclosure, a method for improvingvision of a subject having an implanted intraocular lens (IOL) caninclude determining parameters of a phase prism to be produced on theIOL to correct negative dysphotopsia, where the determining comprisingdefining the phase prism based on power of the IOL and extension of theprism from respective outer edges of the IOL to the center of the IOL.The method can also include applying a plurality of focused laser pulsesto the IOL at the selected areas, where the laser pulses are configuredto produce, through refractive index writing on the IOL, the phase prismhaving the determined parameters in at least one outermost portionproximate the outer edges of the IOL. In some embodiments, the phaseprism, as produced by the MW on the IOL, is configured to graduallydeviate a chief ray to correct a discontinuity in ray deviation betweenrays missing the IOL and rays being refracted by the IOL.

Personalized Correction of Higher Order Aberrations

The average cornea has +0.27 μm spherical aberration at a 6 mm pupil.Correcting this average spherical aberration can increase contrastsensitivity and, among other benefits, improve a subject's drivingsafety. However, the average root mean square of higher orderaberrations is around 0.5 μm. In accordance with some embodiments of thepresent disclosure, correcting for individual, subject-specific higherorder aberrations can be accomplished through the use of refractiveindex writing on the IOL, since IOL placement is final and will notmove.

In accordance with some embodiments of the present disclosure, aniterative corrective approach is performed to address higher orderaberrations. In some embodiments, the iterative approach includes thesteps of: 1) measuring the subject's higher-order aberrations; 2)calculating the difference (from the current state) to a desired higherorder aberration profile, and 3) producing the desired higher orderaberration profile via refractive index writing. Steps 1 to 3 can berepeated until the desired profile is reached in a closed loopiteration. The step of measuring the higher-order aberrations, and thestep of calculating the difference, can be performed at least in partusing a wavefront sensor, for example a Hartmann-Shack wavefront sensor.

In some embodiments, correction of circularly symmetric aberrations suchas spherical aberration can be performed through selectively alteringthe zone width depending on radius and angle of the IOL position, andcircularly asymmetric aberrations can be corrected by altering the zonewidth depending on angular location. As an example implementation, thecorrection of personalized higher order aberrations can significantlyimprove the visual outcomes subjects implanted with spherical IOLs (whotend to have large amounts of positive spherical aberrations).

Consistent with one or more aspects described above, and in accordancewith some embodiments of the present disclosure, a method for improvingvision of a subject having an implanted intraocular lens (IOL) caninclude performing an iterative, closed-loop correction process tocorrect one or more of the higher order aberrations of the subject. Insome embodiments, the closed-loop correction process includes measuringthe higher order aberrations associated with the vision of the subjectand determining, based at least in part on the measurements, a targethigher order aberration correction that can be at least one of: fullcorrection of at least one of the higher order aberrations of thesubject; partial correction of at least one of the higher orderaberration of the subject; and induction of at least one higher orderaberration. The method also includes applying a plurality of focusedlaser pulses to selected areas of the IOL, where the laser pulses areconfigured to produce, through refractive index writing, a target higherorder aberration correction profile on the IOL.

In some embodiments, the method also includes a closed-loop method thatincludes the steps of determining if the produced correcting profilemeets the determined profile and, responsive to determining that theproduced correcting profile does not meet the determined profile:measuring the difference between the higher order aberrations profile ofthe eye after the laser treatment and the target higher orderaberrations correction and using this information to calculate thedetermined profile to achieve the target higher order aberrationcorrection, and, based at least in part on the measured difference,applying a plurality of focused laser pulses to the IOL for refractiveindex writing, where the configuration of the laser pulses are modifiedfrom the prior applied laser pulses based on the measured difference,and repeating the above steps until the produced higher order aberrationcorrecting profile meets the determined target higher order aberrationcorrection.

Ocular Diseases

Ocular diseases are often gradual and occur with advanced age, aftercataract surgery has been performed. Ocular diseases can cause loss incentral visual performance (e.g., age-related macular degeneration) orat more peripheral locations (e.g., glaucoma). In accordance with someaspects of the present disclosure, there are several treatmentmodalities utilizing refractive index writing to address oculardiseases.

A common factor for many ocular diseases is an increased need for ocularcontrast. There are different ways to improve the contrast in thesesubjects, using refractive index writing in accordance with embodimentsof the present disclosure. In some embodiments, these ways ofimprovement include one or more of inscribing correction of longitudinalchromatic correction through a diffractive pattern to increase contrast,and by correcting higher order aberrations.

Macular degeneration is an ocular disease known to cause retinal damage.According to some embodiments of the present disclosure, refractiveindex writing is utilized to cause a yellowing of the IOL such that moreharmful short wavelength light rays are absorbed, which is particularlybeneficial for further preventing retinal damage caused maculardegeneration. Subjects with macular degeneration can experience apositive magnification in vision that makes the world appear bigger. Onthe other hand, subjects with, for example glaucoma or hemianopia maybenefit from a minification, making the world smaller, since they cansuffer from a loss of outer peripheral vision which makes navigationmore difficult, and a minified view of the world can fit more of thevisual field within their functioning vision. It is known that wearingspectacles with a positive power results in a magnified view of theworld, and that wearing negative spectacles results in a minified viewof the world. In some embodiments of the present disclosure, refractiveindex writing is used to produce a refractive outcome needing eitherpositive or negative spectacle correction, to have the desired effectfor the refractive outcome and spectacle magnification. Subjects withcertain ocular diseases may suffer from reduced quality of peripheralvision. In accordance with some embodiments of the present disclosure,gradient-index patterns can be applied to an implanted IOL by refractiveindex writing.

According to one aspect, the present disclosure relates to a method forimproving vision of a subject having an implanted intraocular lens(IOL). The method can include: determining visual needs of a subjectthat are associated with an ocular disease of the subject anddetermining a pattern of a plurality of pulses of radiation (e.g.,plurality of focused laser pulses) to apply, by refractive indexwriting, to one or more selected areas of the IOL. The plurality ofpulses can be configured to induce a change in the implanted IOL toadapt the optical performance of the IOL to at least one of the visualneeds of the subject. The method can also include applying, according tothe determined pattern, the plurality of pulses of radiation to the oneor more selected areas of the IOL.

In some embodiments, adapting the optical performance of the IOL to thevisual needs of the subject can include increasing ocular contrast byinscribing a diffractive pattern in the IOL that is configured tocorrect longitudinal chromatic aberration. In some embodiments, adaptingthe optical performance of the IOL to the visual needs of the subjectcan include increasing ocular contrast by correcting a higher-orderaberration.

Adapting the optical performance of the IOL to the visual needs of thesubject can additionally or alternatively include one or more of:producing a yellowing of at least a part of the IOL, wherein shortwavelength light rays are absorbed; modifying the power of the IOL tocorrect for residual refractive errors (e.g., defocus and astigmatism);modifying the power of the IOL to improve vision for a given distance(e.g., far correction, near correction, intermediate correction);modifying the phase profile of the IOL to remove an existing diffractiveor multifocal refractive profile in the IOL; modifying the phase profileof the IOL to redirect the light passing through the IOL to thesubject-preferred retinal location (PRL); and/or inducing agradient-index pattern on the IOL that is configured to improveperipheral vision of the subject.

In some embodiments, the residual refractive error can be a residualspherical error associated with an uncorrected astigmatism, anddetermining the pattern of the plurality of pulses of radiation to applycan include calculating a radius of a phase shift for correcting for aresidual spherical error. The radius can be calculated according tofactors that include an angular dependence. The radius of the phaseshift can be calculated, at least in part, according to:

$r = \sqrt{m\frac{2\lambda}{F_{1} + {\left( {F_{2} - F_{1}} \right){{\sin \; \theta}}}}}$

where λ is the wavelength, m is a natural number, θ is the angle, and F1and F2 the power to be corrected in the respective meridians.

In some embodiments, adapting the optical performance of the IOL to thevisual needs of the subject can include determining parameters of aphase prism to be produced on the IOL to correct negative dysphotopsiaof the subject. Determining the parameters can include defining thephase prism based on power of the IOL and extension of the prism fromrespective outer edges of the IOL to the center of the IOL. Determiningthe pattern of a plurality of pulses of radiation to apply can includedetermining a pattern of a plurality of pulses of radiation to apply toproduce, through refractive index writing on the IOL, wherein the phaseprism has the determined parameters. In some embodiments, the one ormore selected areas of the IOL include at least one outermost portionproximate the outer edges of the IOL. In some embodiments, the phaseprism, as produced on the IOL, is configured to gradually deviate achief ray to correct a discontinuity in ray deviation between raysmissing the IOL and rays being refracted by the IOL.

In another aspect, the present disclosure relates to a system fortreating an ocular disease of a subject having an implanted intraocularlens (IOL). In some embodiments, the system can include a pulsed lasersystem configured to apply, according a determined pattern, a pluralityof focused laser pulses to one or more selected areas of the IOL. Thesystem can also include a control system coupled to the pulsed lasersystem and configured to control the pulsed laser system to apply theplurality of focused laser pulses. The control system can also beconfigured to: determine visual needs of a subject that are associatedwith an ocular disease of the subject; and determine the pattern of aplurality of laser pulses to apply, by refractive index writing, to theone or more selected areas of the IOL. The plurality of laser pulses canbe configured to induce a change in the implanted IOL to adapt theoptical performance of the IOL to the visual needs of the subject.

In some embodiments, adapting the optical performance of the IOL to thevisual needs can include increasing ocular contrast by inscribing adiffractive pattern in the IOL that is configured to correctlongitudinal chromatic aberration. In some embodiments, adapting theoptical performance of the IOL to the visual needs can includeincreasing ocular contrast by correcting a higher-order aberration. Insome embodiments, adapting the optical performance of the IOL to thevisual needs can include producing a yellowing of at least a part of theIOL, wherein short wavelength light rays are absorbed.

In some embodiments, adapting the optical performance of the IOL to thevisual needs can include modifying the power of the IOL to correct forat least one residual refractive error. The at least one residualrefractive error can include defocus and/or astigmatism. In someembodiments, he at least one residual refractive error can be a residualspherical error associated with an uncorrected astigmatism.

In some embodiments, determining the pattern of the plurality of laserpulses to apply can include calculating a radius of a phase shift forcorrecting for a residual spherical error. The radius can be calculatedaccording to factors that include an angular dependence. In someembodiments, the radius of the phase shift can be calculated, at leastin part, according to:

$r = \sqrt{m\frac{2\lambda}{F_{1} + {\left( {F_{2} - F_{1}} \right){{\sin \; \theta}}}}}$

where λ is the wavelength, m is a natural number, θ is the angle, and F1and F2 the power to be corrected in the respective meridians.

In some embodiments, adapting the optical performance of the IOL to thevisual needs can include modifying the power of the IOL to improvevision for a given distance. In some embodiments, adapting the opticalperformance of the IOL to the visual needs can include modifying thephase profile of the IOL to remove an existing diffractive or multifocalrefractive profile in the IOL. In some embodiments, adapting the opticalperformance of the IOL to the visual needs can include modifying thephase profile of the IOL to redirect light passing through the IOL tothe subject's preferred retinal location (PRL). In some embodiments,adapting the optical performance of the IOL to the visual needs caninclude inducing a gradient-index pattern on the IOL that is configuredto improve peripheral vision of the subject.

In some embodiments, adapting the optical performance of the IOL to thevisual needs can include determining parameters of a phase prism to beproduced on the IOL to correct negative dysphotopsia of the subject; thedetermining can include defining the phase prism based on power of theIOL and extension of the prism from respective outer edges of the IOL tothe center of the IOL. Determining the pattern of laser pulses to applycan include determining a pattern of a plurality of laser pulses toapply to produce, through refractive index writing on the IOL, the phaseprism having the determined parameters.

In some embodiments, the one or more selected areas of the IOL caninclude at least one outermost portion proximate the outer edges of theIOL. In some embodiments, the phase prism, as produced on the IOL, canbe configured to gradually deviate a chief ray to correct adiscontinuity in ray deviation between rays missing the IOL and raysbeing refracted by the IOL.

IOL Positioning

The eye is not a perfectly centered optical system. The apex of thecornea, center of the pupil, center of the IOL and fovea does not alwaysfall along a straight line. Furthermore, even if there is such a line,the optical elements can be tilted with respect to that line. Thesedeviations from un-tilted straight-line optics have many names,depending on which of these deviations is taken as a reference point(e.g., center of pupil, fovea, or corneal apex) which include anglekappa, angle alpha, angle lambda and angle gamma. When the cornea,pupil, IOL, and fovea, all of which can be decentered and two of whichhave an optical impact of tilt (cornea and IOL), a large number ofdeviations can exist, and therefore even perfect positioning and tilt ofthe IOL during surgery may not result in optimal vision. FIG. 5A is anillustration of an eye of a subject with a tilted IOL (note thealignment along the dashed line, which is tilted with respect to theoptical axis OA, rather than the optical axis), and FIG. 5B is anillustration of an eye of a subject with the IOL decentered with respectto the optical axis OA (note the vertical displacement of the IOL abovethe optical axis OA, as further indicated by the dashed line). In eachof FIGS. 5A and 5B, like elements of the eye and IOL shown in FIG. 1Bshare the same reference numerals. FIG. 6A illustrates a phase map (inwaves) of a 20 D monofocal IOL implanted in an average eye. FIG. 6Billustrates the phase map (in waves) induced by 5 degrees tilt of a 20 Dmonofocal IOL. FIG. 6C illustrates the phase map (in waves) induced by0.5 mm decentration of a 20 D monofocal IOL.

In accordance with some embodiments of the present disclosure,refractive index writing is used to optimize foveal vision by correctingfor the effect of these deviations in position by inscribing phasepattern on the IOL that corrects and compensates for these errors. Theposition and tilt of each of the elements can be measured after surgery,and ray-tracing software can be used to calculate the optimal aberrationpattern inscribed which corrects for these errors.

Tilt and decentration can be altered by phase changes from refractiveindex writing. These can be measured using, for example, Purkinjeimaging technology. Subsequently, the impact of tilt and decentration onIOLs can be simulated using ray tracing software, and adequate phase mapcompensation then calculated accordingly. This can be done once for awide range of IOL models, tilt, and decentration, to provide automaticsuggestion of phase changes following a measured tilt and decentration.Examples of ray-tracing software are Zemax and Oslo. In them, eye modelscan be implemented (such as the Navarro eye model). Normally, lenses arewell-centered, but if the IOL is simulated to be decentered according tomeasured values, and subsequently a phase map is imposed, the softwarecan optimize which phase map provides the best vision by optimizing forproviding, for example, the best modulation transfer function (MTF).

In one aspect, the present disclosure relates to a method for improvingvision of a subject having an implanted intraocular lens (IOL). In oneembodiment, the method can include determining a deviation in positionof at least one optical element from a reference line corresponding toalignment of the apex of the cornea, center of the pupil, center of theIOL, and fovea, and/or determining a tilt of at least one of the opticalelements relative to the reference line. The deviation(s) in positionand the tilt produce an imperfection in foveal vision in the subject.The method can further include applying a plurality of focused laserpulses to a selected area of the implanted IOL, using laser pulses thatare applied according to a predetermined pattern and that are configuredto produce, through refractive index writing, a phase change pattern onthe IOL that is configured to compensate for the deviation(s) and/ortilt to improve the foveal vision of the subject.

The phase change pattern to be produced by RIW can be calculated, priorto the application of the plurality of focused laser pulses, based on atleast one of: biometrics including one or more of IOL positioning, axiallength, corneal power, and refraction. The biometrics associated withthe IOL positioning include measurements of at least one of effectivelens position, tilt, and decentration of the IOL. The biometricsassociated with the corneal power can include keratometry and/orelevation maps.

In some embodiments, determining the tilt and decentration can beperformed using Purkinje imaging. In some embodiments, determining thetilt and decentration can performed using optical coherence tomography(OCT). In some embodiments, determining the phase change pattern caninclude ray-tracing simulation.

In some embodiments, the pattern according to which the pulses ofradiation are applied can be calculated based at least in part on the atleast one of the deviation in position and the tilt.

In another aspect, the present disclosure relates to a system forimproving vision of a subject. In one embodiment, the system includes atleast one sensor that is configured to sense a deviation in position ofat least one optical element from a reference line corresponding toalignment of the apex of the cornea, center of the pupil, center of theIOL, and fovea and/or a tilt of at least one optical element relative tothe reference line. The deviation in position and/or the tilt producesan imperfection in foveal vision in the subject. The system alsoincludes a control system operatively coupled to the at least one sensorand configured to receive associated sensed data corresponding to thedeviation in position and/or the tilt. The control system is alsoconfigured to calculate, based at least on the sensed data, a phasechange pattern to produce on the IOL, that is configured to compensatefor the deviation and/or tilt to improve the foveal vision of thesubject. The control system is also configured to calculate a pattern ofa plurality of pulses of radiation to apply to the IOL to produce thephase change pattern and/or calculate one or more selected areas of theIOL to which the plurality of pulses are to be applied. The system alsoincludes a pulsed radiation system operatively coupled to the controlsystem. The pulsed radiation system can be configured to, based oncontrol by the control system, apply the plurality of pulses ofradiation to the IOL according to the pattern to produce, by refractiveindex writing on the IOL, the phase change pattern on the IOL that isconfigured to compensate for the deviation and/or tilt to improve thefoveal vision of the subject. The at least one sensor can be configuredto sense the deviation and tilt and the control system may be configuredto receive data corresponding to both the deviation and the tilt.

In some embodiments, the pulsed radiation system includes a pulsed laserand is configured to apply a plurality of laser pulses to the one ormore selected areas of the IOL, according to the pattern of theplurality of pulses, to produce the phase change pattern. In someembodiments, the control system can be configured to determine the phasechange pattern based at least in part on biometrics associated with atleast one of: IOL positioning; axial length; corneal power; andrefraction. In some embodiments, the biometrics associated with IOLpositioning include measurements of at least one of effective lensposition, tilt, and decentration of the IOL. In some embodiments, thebiometrics associated with the corneal power include at least one ofkeratometry and elevation maps.

In some embodiments, the system can be configured to determine the tiltand/or decentration using Purkinje imaging. In some embodiments, thesystem also includes an optical coherence tomography (OCT) systemconfigured to determine the tilt and/or decentration. In someembodiments, the system is configured to determine the phase changepattern using, at least in part, ray-tracing simulation. In someembodiments, the control system can be configured to calculate thepattern according to which the pulses of radiation are applied based atleast in part on the deviation in position and/or the tilt.

Phase Wrapping

Phase wrapping relates to, in the implementation of refractive indexwriting, that the maximum achievable optical path difference can belimited. For example, a refractive index writing system may not be ableto easily shift the phase, e.g., 1.5 wavelengths, 2 wavelengths, or 3wavelengths, at various locations in an intraocular lens (IOL), as thereis a maximum possible shift in the absolute value of the refractiveindex over a volume. In some cases, the upper limit can be 1 wavelength,which may cause a challenge in implementing various phase maps. Phasewrapping in accordance with some embodiments of the present disclosurecan overcome such challenges.

The starting point of a desired refractive index implementation,including those described above in accordance with certain embodimentsof the present disclosure, is a phase map that has been shown to, e.g.,shift power, reduce residual astigmatism, improve near vision, improvespectacle independence or reduce visual symptoms. Such phase maps oftencontain values higher than one wavelength. In these implementations,such higher values can be modulated by subtracting the necessary numberof whole wavelengths in the phase step such that the complete phase maphas values in the range of zero to one wavelength.

An example of the consequence of this implementation can be seen in FIG.7. FIG. 7 plots the optical path difference of an implemented refractiveindex design with certain parts of the phase map having a phase additionhigher than one wavelength. For the parts of the design that have aphase addition lower than one wavelength, no difference is seen. For theparts of the original design with a phase map value higher than onewavelength, however, a difference of exactly one wavelength (e.g. at 0.7mm radius, at 1 mm radius, and at 1.3 mm radius) can be seen.Furthermore, the optical path difference impact of the transitionbetween different zones can be seen. It should be understood that thisexample is purely for illustrative purposes, and any number of zones,and whole number of wavelengths can be phase wrapped.

Benefits of the use of phase wrapping in accordance with someembodiments can be seen in the comparison of the illustrations of FIGS.8A-8C. In each of FIGS. 8A-8C, three cases are compared: the designimplemented using a sag profile (standard IOL technology), design usingrefractive index writing without the one wavelength limitation, andrefractive index writing using phase wrapping. As is evident from theillustrations, phase wrapping successfully replicates the performanceboth of the sag profile and of the full refractive index writingprofile.

Consistent with one or more aspects described above, and in accordancewith some embodiments of the present disclosure, a method for phasewrapping in refractive index writing of an intraocular lens (IOL)implanted in a subject includes: for at least one area of the IOLwherein there is a maximum possible shift in the absolute value of therefractive index over a particular volume, modulating the values of acorresponding phase map such that the phase map has values in aparticular desired wavelength range. In some embodiments, the desiredwavelength range is from about 0 to about 1 wavelength for a maximumpossible shift in the absolute value of above 1 wavelength of therefractive index over the particular volume.

Vergence Matching

In refractive index writing, in some implementations phase maps may notbe implemented in narrow layers, but rather wide layers of, e.g., 50 μm,100 μm, 200 μm, or 300 μm. This is wider than for sag profiles. As aresult, light that is incident at a vergence, which is the case in theeye, risks transitioning from one zone to the other. For example, at onezone the desired phase addition can be 1.5 wavelength, and close by thedesired phase addition can be 0 wavelengths. However, due to thevergence of the light, if the zone has a width of 300 μm, during thefirst 150 μm the light can pass the zone of 0 wavelengths phaseaddition, and during the last 150 μm the light can pass the zone of 1.5wavelengths phase addition, with the result that the light has a phaseaddition of 0.75 wavelengths. This can result in undesirable outcomesfor the subject.

To address the above-mentioned concerns, in some embodiments of thepresent disclosure a vergence matching is implemented in the refractiveindex writing. A vergence matching starts with a desired phase map, andinitial depth position in the IOL, as well as the distance between theIOL and the retina. In some embodiments, the following steps are thenperformed: 1. creating a transformation function based on the vergenceof the incident light; and 2. creating an angulated phase addition.

In accordance with some embodiments, creating a transformation functionbased on the vergence of the incident light includes mapping, as afunction of radius in the IOL, the shift in z direction necessary tomatch the spherical form of the idealized wave when inside the IOL. Thiscan be calculated by: a) taking an object at infinity, b) imagingthrough the subject's individual cornea, c) propagating to the anteriorsurface of the desired IOL using the measured anterior chamber depth(ACD) of the subject, d) imaging through the anterior surface of theIOL, and e) propagating to the plane of the desired refractive indexwriting. The wave will have a vergence, and this vergence is matchedwith the baseline surface of where the zero-level of the refractiveindex pattern is written.

In other embodiments, an average eye model (average cornea and/oraverage ACD) can be used to calculate the vergence. In otherembodiments, a combination of measured and average data can be used tocalculate vergence. Additionally, vergence matching can account for bothrotationally and non-rotationally optical effects, by creating a 2Dfunction, where vergence is determined by meridian.

With regard to the above-mentioned step “2.” of creating an angulatedphase addition, while the phase pattern can be written perpendicular tothe apex of the IOL, in accordance with some embodiments of the presentdisclosure at each point in this new surface described at point 1, thephase map is instead written with a depth of, e.g., 50 μm, 100 μm, 200μm, or 300 μm perpendicular to the vergence calculated above. Theadvantages of vergence matching according to some embodiments of thepresent disclosure can be seen in the comparison of simulations shown inFIGS. 9A and 9B, illustrating simulations with and without vergencematching, utilizing refractive index written designs.

Consistent with one or more aspects described above, and in accordancewith some embodiments of the present disclosure, a method for vergencematching in refractive index writing includes determining a desiredphase map for producing, by refractive index writing, a phase change onan IOL, which can be an IOL implanted in the eye of a subject;determining the vergence of the wave after refraction on the anteriorsurface of the IOL for the design wavelength; propagating this wavefrontto the plane of the refractive index writing within the IOL, andestimating the curvature in that plane. Based on this result, a desiredphase map can be converted into a vergence-matched three-dimensional(3D) phase map such that the original flat phase map follows the curvedvergence of the wavefront. Estimating the curvature in the plane of therefractive index writing can include calculating the curvature using raytracing software (e.g., Zemax, Code V, Oslo), or other geometricaloptics calculations (e.g., relating to wave propagation), some aspectsof which will be described below.

Propagation of the wavefront can be calculated by: taking an object atinfinity; imaging through the individual cornea of the subject;propagating to the anterior surface of the IOL based on a measureddistance between the cornea of the subject and the anterior surface ofthe IOL, the shape of the anterior surface of the IOL, and therefractive index of the IOL; imaging through the anterior surface of theIOL; and propagating to the plane inside the IOL to an area where therefractive index writing is to be performed. In some embodiments, themethod includes matching the vergence with a baseline surface where thezero-level of the refractive index pattern is written. The vergence canbe calculated using a model of an average cornea and/or average ACD. Thevergence can be calculated using a model of an average IOL design for aparticular power. The shape of the anterior surface of the IOL can beestimated using optical coherence tomography (OCT) imaging.

In some embodiments, vergence matching accounts for rotational andnon-rotational optical effects by creating a two-dimensional function,wherein vergence is determined by meridian. In some embodiments, themethod also includes creating an angulated phase addition, wherein ateach point on a target surface of the IOL, a phase addition is written,by the refractive index writing, with a depth perpendicular to thecalculated vergence. The phase addition can have a predetermined depthperpendicular to the calculated vergence. The refractive index writingcan include applying a plurality of focused laser pulses to a selectedarea of the IOL.

In another aspect, the present disclosure relates to a system forimproving vision of a subject. In one embodiment, a pulsed radiationsystem can be configured to apply, by refractive index writing, aplurality of pulses of radiation to at least one selected area of anintraocular lens (IOL) implanted in an eye of a subject, according to apredetermined pattern. The system can also include a control systemcoupled to the pulsed radiation system and configured to control thepulsed radiation system and to perform functions that include:determining a desired phase map for producing, by refractive indexwriting, a phase change in an IOL implanted in an eye of a subject, theIOL having an anterior surface and a posterior surface; calculatingvergence of a wave after refraction on the anterior surface of the IOLfor a desired wavelength design; calculating propagation of acorresponding wavefront to the plane of the refractive index writingwithin the IOL; estimating curvature of the wavefront in the plane ofthe refractive index writing; and, based on the estimated curvature,converting an initial phase map into a vergence-matchedthree-dimensional (3D) phase map, such that the initial phase mapfollows the curved vergence of the wavefront; and

In some embodiments, propagation of the wavefront can be calculated byperforming functions that include: taking an object at infinity; imagingthrough the individual cornea of the patient; propagating the wavefrontto the anterior surface of the IOL based on a measured distance betweenthe cornea of the patient and the anterior surface of the IOL, the shapeof the anterior surface of the IOL, and the refractive index of the IOL;imaging through the anterior surface of the IOL; and propagating thewavefront to the plane inside the IOL to an area where the refractiveindex writing is to be performed. The vergence can be matched with abaseline surface wherein the zero-level of the refractive index patternis written.

In some embodiments, a model of an average cornea and/or averageanterior chamber depth (ACD) is used to calculate the vergence. In someembodiments, a model of an average IOL design for a particular power isused to calculate the vergence. In some embodiments, the shape of theanterior surface of the IOL can be estimated using optical coherencetomography (OCT) imaging In some embodiments, the vergence matchingaccounts for rotational and non-rotational optical effects by creating atwo-dimensional function, wherein vergence is determined by meridian.

In some embodiments, the control system can be configured to control thepulsed radiation system to create an angulated phase addition, whereinat each point on a target surface of the IOL, a phase addition iswritten, by the refractive index writing, with a depth perpendicular tothe calculated vergence. In some embodiments, the phase addition has apredetermined depth perpendicular to the calculated vergence.

Vergence Matching of a Refractive Index Writing Design

FIGS. 10A-C illustrate aspects of vergence matching of a refractiveindex writing design, in accordance with embodiments of the presentdisclosure. FIG. 10A shows a schematic of the pseudo-phakic eye (see,e.g. cornea 1002 and retina 1012) with rays entering the eye with zerovergence, as well as an intraocular lens (IOL) 1008 comprising anoptical profile 1010 induced by refractive index writing, collectively1000. FIGS. 10B and 10C show a zoomed in view of the optical profile1010. In accordance with some embodiments of the present disclosure, todesign a lens that considers the vergence of the wavefront 1004 (λ₀),for the design wavelength, the direction (tan(θ)) of each ray ismeasured at a given radial coordinate. FIGS. 10B and 10C show also thatthe direction of the ray increases with the radial coordinates. Inaccordance with some embodiments, knowing the ray direction versus rayheight and the value of the refractive index (RI) at RI (z₀, R₀) (seeFIG. 10B)), the refractive index is redesigned inside such that the RIat (z₁, R₁) is equal to the RI at (z₀, R₀) (see FIG. 10B). Accordingly,the z-dependence is achieved by making the RI at (z₀, R₀) equal to theRI at (z₁, R₁); this thereby “shrinks” or reduces the volume where therefractive index has been written. To keep the rays shown in FIG. 10Bfrom deviating or changing direction, the optical profile 1010 is bent(see FIG. 10C, bent with reference to the initial orientation indicatedby the dashed box) such that these rays have a zero incidence.

Further stated, FIG. 10B shows that the output rays after the opticalprofile 1010 with vergence matching are parallel to the ray beforeentering the optical profile 1010 with an offset. This can cause anunwanted spherical aberration, longer optical path length than intended,and/or un-intended power shift, among other undesired effects. To cancelthese undesirable effects, in accordance with some embodiments, thesurfaces (anterior 1010 a and posterior 1010) of the optical profile1010 are bent such that the rays at the interface between the IOL 1008and optical profile 1010 have a zero incidence, i.e., the rays arenormal to the surface of the optical profile 1010 (see FIG. 10C).Therefore, the rays do not change their direction inside and outside theoptical profile 1010 and add the intended optical path length.

Consistent with aspects described above, and in accordance with someembodiments of the present disclosure, a method of vergence matching foran intraocular lens (IOL) having an optical profile induced byrefractive index writing can include the steps of: determining thedirection of a plurality of rays associated with a vergence of awavefront; determining the ray direction and ray height of a pluralityof rays entering a first location of the optical profile; anddetermining the refractive index of the optical profile at the firstlocation. The method can also include, based on the determined raydirection, ray height, and refractive index at the first location, andby refractive index writing, specifying the volume and shape of eachvoxel to match the wavefront through the direction of propagation. Themethod can also include bending anterior and posterior surfaces of theoptical profile such that rays inside a portion of the IOL changed byrefractive index writing and outside a portion of the IOL changed byrefractive index writing do not change direction; and determining asecond location that, for each of the rays, corresponds to the locationwhere the respective ray exits the optical profile changed by refractiveindex writing.

In some embodiments, the volume and shape of each voxel match thewavefront through the direction of propagation such that the voxelsdecrease for converging wavefronts. In some embodiments, the volume andshape of each voxel match the wavefront through the direction ofpropagation such that the voxels increase for diverging wavefronts.

In some embodiments, the anterior and posterior surfaces of the opticalprofile are bent such that rays at the interface of the respectivesurfaces of the optical profile with other portions of the lens have azero incidence. The first location can correspond to a first planeparallel to a vertical axis of the lens and the second location cancorrespond to a second plane parallel to the first plane. The firstlocation can be proximate to or correspond to the anterior surface ofthe lens and the second location can be proximate to or correspond tothe posterior surface of the lens. In some embodiments, the bentanterior and posterior surfaces are bent to define a non-zero curvatureabout the optical axis. In some embodiments, the refractive indexwriting includes applying a plurality of pulses of radiation accordingto a predetermined pattern. The plurality of pulses of radiation can befocused laser pulses applied according to the predetermined pattern. Insome embodiments, the IOL is implanted in an eye of a subject.

In another aspect, in some embodiments a system for improving vision ofa subject can include a pulsed laser system configured to apply aplurality of laser pulses to an intraocular lens (IOL) implanted in aneye of a subject and to change the refractive index of at least oneselected area of the IOL by refractive index writing, wherein the IOLhas an optical profile induced by refractive index writing. The systemcan also include a control system coupled to the pulsed laser system andconfigured to control the pulsed laser system to apply the plurality oflaser pulses according to calculated pattern. The control system canalso be configured to perform functions that include determining thedirection of a plurality of rays associated with a vergence of awavefront; determining the ray direction and ray height of a pluralityof rays entering a first location of the optical profile; determiningthe refractive index of the optical profile at the first location; and,based on the determined ray direction, ray height, and refractive indexat the first location, and by refractive index writing using the pulsedlaser system, specifying the volume and shape of each voxel to match thewavefront through the direction of propagation.

In some embodiments, the control system can also be configured tocalculate the pattern of laser pulses to apply. In some embodiments,anterior and posterior surfaces of the optical profile are bent suchthat rays inside a portion of the IOL changed by refractive indexwriting and outside a portion of the IOL changed by refractive indexwriting do not change direction. In some embodiments, the control systemcan be further configured to determine a second location that, for eachof the rays, corresponds to the location where the respective ray exitsthe optical profile changed by refractive index writing. In someembodiments, the volume and shape of each voxel match the wavefrontthrough the direction of propagation such that the voxels decrease forconverging wavefronts. In some embodiments, the volume and shape of eachvoxel match the wavefront through the direction of propagation such thatthe voxels increase for diverging wavefronts.

In some embodiments, the anterior and posterior surfaces of the opticalprofile are bent such that rays at the interface of the respectivesurfaces of the optical profile with other portions of the lens have azero incidence. In some embodiments, the anterior and posterior surfacesare bent to define a non-zero curvature about the optical axis.

In some embodiments, the first location can correspond to a first planeparallel to a vertical axis of the lens and the second locationcorresponds to a second plane parallel to the first plane. In someembodiments, the first location can be proximate to or corresponds tothe anterior surface of the lens, and the second location can beproximate to or corresponds to the posterior surface of the lens.

FIGS. 11 and 12 illustrate the radial dependence of the refractive indexchange for different thicknesses of the optical profile written insidethe IOL, for power subtraction (FIG. 11) and power addition (FIG. 12),in accordance with embodiments of the present disclosure. FIGS. 13 and14 illustrate the radial dependence of the refractive index change fordifferent thicknesses of the optical profile written inside the IOL forspectacle independence, for negative added power (FIG. 13) and positiveadded power (FIG. 14), in accordance with embodiments of the presentdisclosure.

FIG. 15 shows results of simulations in an anatomically correct eyemodel using ray tracing software (Zemax) illustrating through frequencyMTF with a comparison between an IOL with a refractive anterior andposterior surface (“refractive”), an IOL with an anterior refractivesurface with refractive index writing without vergence matching(“grin_standard”), and an IOL with vergence matching according to someembodiments of the present disclosure(“refractive_grin_with_vergence_matching”). “Polychromatic” and “4.5 mmstop” refers to a simulation condition of MTF for white light(polychromatic) and a 4.5 mm pupil diameter. FIG. 16 shows the resultsof simulations in TCEM illustrating through frequency MTF (FIG. 16) andthrough focus MTF at 50 c/mm (FIG. 17), with a comparison between an IOLwith a refractive anterior and posterior surface (“refractive”), an IOLwith refractive index writing without vergence matching(“grin_standard”), an IOL like the grin_standard, but with therefractive index shrunk along the z axis in accordance with vergencematching in some embodiments described above (“grin_shrink”), and an IOLwith refractive anterior and diffractive, elevated, posterior surface(“diffractive sag”).

FIGS. 18 and 19 show results illustrating a similar comparison fornormalized polychromatic point spread function (PSF) (FIG. 18) andpolychromatic halo simulation (FIG. 19). Rather than describing theoptical quality, as measured by MTF, these Figures show simulatedaspects of the perception of visual symptoms (e.g., halo). As a PSF, anideal would be to have all energy go to a single point, that of 0; it isdesired to have a high up peak to the left of the curve, and thenimmediately the intensity going down; so for the rest of the curve,higher and higher up means a worse and worse perceived halo;“refractive” is lower than others. As further shown, “grin shrink” isparticularly good in this aspect. FIG. 20 shows simulated haloperformance for a number of different designs: that of a standardrefractive IOL (“refractive”), that of an extended depth of focusembodiment with vergence matching (“grin shrink”), that of an extendeddepth of focus embodiment IOL implemented with normal refractive indexwriting (grin standard), and the same extended depth of focus embodimentachieved by standard methods of elevated posterior surface (diffractivesag).

Multi-Layer IOL

According to certain aspects, the present disclosure relates topost-surgically improving vision in a subject with an implantedintraocular lens (IOL) through the use of refractive index writing and aflexible, multi-layered gradient index approach, such as to produce aneffect like that produced by a GRIN lens. In some embodiments, themulti-layered approach is not diffractive; rather, it is purelyrefractive, without transition steps; the multi-layered approach cancreate a long series of transitions rather than a single surface. Apower shift can occur not only at anterior and posterior sides of anIOL, but multiple times inside the lens, and without relying ondiffractive aspects. In various embodiments, the multiple layers areinduced inside the lens at different depths by focusing applied laserradiation at particular selected depths, through changing, e.g.,settings and exposure times. The laser can be used to directly reach thedesired state, going directly from a starting index of refraction to thedesired index of refraction for a particular layer. Accordingly, thereis not a restriction on a particular sequence in terms of depths orother progression that must be followed; for instance, one can startwith an innermost layer, outermost, or any in between.

In accordance with some embodiments, in order to induce a layer in theIOL, a voxel-based treatment of the IOL is applied, wherein as one goessequentially through each voxel, the desired shift in refractive indexis applied, determined by total amount of light energy focused in theparticular area and the duration of focus time. Whereas in some otherapproaches, for each (x,y) coordinate on the IOL, a uniform shift inrefractive index is created over the full range of z where it is applied(i.e., the depth, for example 100 microns, 200 microns, or 400 microns);instead, in accordance with aspects of the multi-layered approachaccording to embodiments of the present disclosure, there are uniformlayers, but changes over z. The depth at which a uniform index ofrefraction change can be produced can be, for example 20 microns, 30microns, or 50 microns.

As discussed above in some detail, factors that can limit a subject'svisual performance post surgery, for example after cataract surgery, caninclude: incorrect IOL power, uncorrected astigmatism, IOL placementerror, higher order aberrations, spectacle dependence, negativedysphotopsia, peripheral aberrations, and chromatic aberrations.

FIG. 21 illustrates a side, cross-sectional view of an IOL along anoptical axis OA, showing the outline of an IOL 2100 (with an anteriorside 2102 a and posterior side 2102 b), the index of refraction of theoriginal IOL n₁ several layers 2104, 2016, 2108, 2110 with variousshapes, and their associated index of refraction (n₁, n₂, n₃, and n₄).In particular, the illustration of FIG. 21 shows the cross-section ofthe IOL 2100 with the solution being rotationally symmetric. Theconstructed layers can also be rotationally asymmetric, allowing thecorrection of astigmatism, higher order aberrations, and otherasymmetric errors. The illustration shows four different refractiveindex values (n₁, n₂, n₃, and n₄). In some embodiments, the change inrefractive index writing can be 0.2, such that up to 40 different suchlayers are achievable. For purposes of clarity in the illustratedembodiment of FIG. 21, four layers 2104, 2016, 2108, 2110 are shown.

In some embodiments, the anterior and posterior sides can be ofdifferent shape, as is seen for the fourth layer 2110, wherein theanterior is curved and the posterior is flat. The thickness can be closeto zero over parts of or all of the layers, as is the case in theanterior side of the interface for the third index change (see left sideof layer 2108 proximate the intersection with the optical axis OA).Further, the potential asymmetry is illustrated by the interface of thesecond layer 2106, which is more curved on the left than on the rightside. The described curves are convex. Alternatively, in someembodiments the curves can be concave as well, which induces a negativepower change when the inner layers have a higher refractive index. Takentogether, this multi-layered approach in refractive index writing allowscontrol and alleviation of a number of the factors limitingpost-surgical vision described above, and as will be specificallydiscussed below in further detail.

Regarding incorrect IOL power, the multi-layer approach according tosome embodiments, described above, allows power changes to be madewithout compromising aberration correction. Furthermore, if the inducedlayers follow a toric pattern, astigmatic errors of the patient can becorrected; these include: corneal astigmatism (anterior and posteriorcornea); surgically induced astigmatism; and/or astigmatism fromdecentration, tilt, and angle kappa. Negative effects of incorrect IOLplacement may also be corrected through the multi-layer approachaccording to some embodiments. In one embodiment, the implementation theIOL position and tilt is measured, and the desired multi-layer solutioncompensating for these errors is implemented with refractive indexwriting. In particular, the patient can receive compensation for thetilt of the IOL by induction of a left-right asymmetry in themulti-layers that have a prismatic effect. This prismatic effect alsocan be applied to the case when the patient suffers from strabismus;using an internal prism, this approach does not suffer from thelimitations that make external prisms unworkable for strabismuspatients. With respect to higher order aberrations, even if lenses couldbe customized with an exact measurement of the higher order aberrationsof the patient, such corrections would not be used; even small amountsof decentration, within the range of normal uncertainty of IOL placement(e.g., 0.1 mm) would induce a mismatch between the correction and theoriginal aberration, losing the benefits of the correction andpotentially worsening it instead. In a postoperative multi-layeredapproach according to certain embodiments, the position is controlledwith a high accuracy, overcoming this obstacle.

Regarding spectacle independence, refractive multi-focal intraocularlenses are often not popular, as uptake is limited by the zonal natureof such designs. For example, if a lens has a high add power in thecenter, but a patient has a very small pupil, the entire pupil of thepatient would have the add power, inducing a loss in distance vision.Diffractive lenses, on the other hand, are pupil-independent but sufferfrom visual phenomena. In a multi-layered refractive index writingapproach to multifocal design in accordance with some embodiments, ameasurement of pupil dynamics under different conditions would precedethe algorithmic construction of the different layers. This allows forcustomization of where add power is created, ensuring near and distancevision for the patient under all lighting conditions.

Some aspects of the present disclosure for construction of a peripheralattenuation zone that removes negative dysphotopsia have been describedabove. In some embodiments, such an attenuation zone, an outerperipheral area (e.g. the outer 0.5 mm) that gradually diminishes thedeviation of the chief ray to zero, can be constructed using refractiveindex writing for the patients reporting negative dysphotopsia. Amulti-layer gradient index approach according to some embodiments alsoallows the reduction of peripheral aberrations such as obliqueastigmatism and coma. This may be a synergistic benefit, combined withthe other approaches described above.

Regarding chromatic aberrations, the normal human eye has approximatelyone diopter of longitudinal chromatic aberrations. While this can bereduced by diffractive designs, doing so can lower image quality. Analternative approach, in accordance with some embodiments, is to utilizerefractive designs, using a number of different refracting elements andAbbe numbers. The different powers and Abbe numbers are realized in themultiple layers created by refractive index writing. A desired featureof the implemented total state is that C/V0+F1/V1+F2/V2+F3/V3+ . . . =0,where C is the corneal power, V0 is the Abbe number of the cornea, (F1,F2, F3 . . . ) the power of the different layers and (V1, V2, V3 . . . )the Abbe numbers.

Consistent with aspects described above, and in accordance with someembodiments of the present disclosure, a method for improving vision ina subject having an implanted intraocular lens (IOL) can includedetermining at least one modification to be made to an IOL implanted ina subject to improve the vision of the subject, wherein the IOL has afirst index of refraction. The method can also include, based on thedetermination, applying laser radiation to at least one selected area ofthe IOL to form, within the IOL, at least one additional layer having adifferent index of refraction than the first index of refraction and aparticular shape within the IOL configured to improve the vision of thesubject.

In some embodiments, the applied laser radiation changes the index ofrefraction of the at least one selected area from the first refractiveindex to the different index of refraction in forming the at least oneadditional layer. The index of refraction of the at least one additionallayer can be uniform throughout the respective layer. The at least oneadditional layer can be formed with a series of transitions within theIOL and/or formed to have a shape defined by portions having differentdepths within the IOL. The at least one additional layer can be formedto have a particular thickness and, when formed, at least one of thelayers has a different thickness than another one of the layers.

In some embodiments, applied laser radiation can include one or moreselected optical energies focused in the at least one selected area andone or more selected durations of exposure of the focused optical energyin the at least one selected area, determined at least in part based onthe determined at least one modification to be made to the IOL. In someembodiments, the at least one additional layer can include more than twoadditional layers, and each of the more than two additional layers canhave a respective index of refraction and be formed with a particularshape within the IOL. The more than two additional layers can include atleast two different shapes.

In some embodiments, the at least one modification to be made to the IOLcan correspond to correcting at least one of incorrect IOL power,uncorrected astigmatism, IOL placement error, higher order aberration,spectacle dependence, negative dysphotopsia, peripheral aberrations, andchromatic aberrations. Applying the laser radiation can include indexwriting with a plurality of focused laser pulses applied to the at leastone selected area of the IOL according to a predetermined pattern. Thepredetermined pattern can be based at least in part on the determined atleast one modification to be made to the IOL.

In another aspect, in some embodiments a method for forming amulti-layered intraocular lens (IOL) can include determining at leastone modification to be made to an IOL to improve the visual performanceof the IOL, where the IOL has a first index of refraction and, based onthe determination, applying laser radiation to the IOL to form, withinthe IOL, at least one additional layer having a different index ofrefraction than the first index of refraction and a particular shapewithin the IOL configured to improve the visual performance of the IOL.

The applied laser radiation can change the index of refraction of the atleast one selected area from the first refractive index to the differentindex of refraction in forming the at least one additional layer. Theindex of refraction of the at least one additional layer can be uniformthroughout the respective layer. The at least one additional layer canbe formed to have a shape defined by portions having different depthswithin the IOL, wherein at least one of the layers has a differentthickness than another one of the layers.

In some embodiments, the applied laser radiation can include one or moreselected optical energies focused in the at least one selected area ofthe IOL and one or more selected durations of exposure of the focusedoptical energy in the at least one selected area, determined at least inpart based on the determined at least one modification to be made to theIOL. Applying the laser radiation can include refractive index writingwith a plurality of laser pulses applied to the at lease one selectedarea of the IOL according to a predetermined pattern. The predeterminedpattern can be based at least in part on the determined at least onemodification to be made to the IOL.

In yet another aspect, in some embodiments a system for improving visionof a subject can include at least one sensor configured to determine acorrection to be made to an intraocular lens (IOL) to improve the visionof a subject, wherein the IOL has a first index of diffraction. Thesystem can also include a control system operatively coupled to the atleast one sensor and configured to receive associated sensed datacorresponding to the correction to be made to the IOL and to calculate,based on the sensed data, shape and/or index of refraction for at leastone additional layer to be formed within the IOL. The additional layercan have a different index of refraction than the first index ofrefraction and a particular shape within the IOL configured to improvethe vision of the subject. Additionally or alternatively, the controlsystem can calculate parameters for a pattern of laser radiation to beapplied to at least one selected area of the IOL to form the at leastone additional layer; and a radiation system operatively coupled to thecontrol system and configured to, based on control by the controlsystem, apply focused laser radiation according to the parameters andpattern of laser radiation to be applied to at least one selected areaof the IOL, to form, within the IOL, the at least one additional layerhaving the different index of refraction and the particular shape.

The calculated parameters for the pattern of laser radiation can includeone or more selected optical energies to be focused in the at least oneselected area and one or more selected durations of exposure for thefocused optical energy in the at least one selected area. The radiationsystem can be a pulsed laser system configured to apply the laserradiation by refractive index writing with a plurality of focused laserpulses applied to IOL according to the calculated parameters andpattern.

In some embodiments, the at least one sensor corresponds to an opticalcoherence tomography (OCT) system configured to determine biometric dataassociated with the correction to be made to the IOL. The applied laserradiation can change the index of refraction of the at least one area ofthe IOL from the first refractive index to the different index ofrefraction in forming the at least one additional layer. The index ofrefraction of the formed at least one additional layer can be uniformthroughout the respective layer. The at least one additional layer canbe formed with a series of transitions within the IOL. The at least oneadditional layer can be formed to have a shape defined by portionshaving different depths within the IOL. The at least one additionallayer can be formed to have a particular thickness, and wherein, whenformed, at least one of the layers can have a different thickness thananother one of the layers.

The various embodiments described above are provided by way ofillustration only and should not be construed to limit the scope of thepresent disclosure. Those skilled in the art will readily recognize thatvarious modifications and changes may be made to the present disclosurewithout following the example embodiments and implementationsillustrated and described herein, and without departing from the spiritand scope of the disclosure and claims here appended and those which maybe filed in non-provisional patent application(s). Therefore, othermodifications or embodiments as may be suggested by the teachings hereinare particularly reserved.

What is claimed is: 1-16. (canceled)
 17. A system for improving visionof a subject, the system comprising: at least one sensor configured todetermine a correction to be made to an intraocular lens (IOL) toimprove the vision of a subject, wherein the IOL has a first index ofdiffraction; a control system operatively coupled to the at least onesensor and configured to receive associated sensed data corresponding tothe correction to be made to the IOL and to calculate, based on thesensed data, at least one of: shape and/or index of refraction for atleast one additional layer to be formed within the IOL, the additionallayer having a different index of refraction than the first index ofrefraction and a particular shape within the IOL configured to improvethe vision of the subject; and parameters for a pattern of laserradiation to be applied to at least one selected area of the IOL to formthe at least one additional layer; and a radiation system operativelycoupled to the control system and configured to, based on control by thecontrol system, apply focused laser radiation according to theparameters and pattern of laser radiation to be applied to at least oneselected area of the IOL, to form, within the IOL, the at least oneadditional layer having the different index of refraction and theparticular shape.
 18. The system of claim 17, wherein the calculatedparameters for the pattern of laser radiation comprise one or moreselected optical energies to be focused in the at least one selectedarea and one or more selected durations of exposure for the focusedoptical energy in the at least one selected area.
 19. The system ofclaim 17, wherein radiation system is a pulsed laser system configuredto apply the laser radiation by refractive index writing with aplurality of focused laser pulses applied to IOL according to thecalculated parameters and pattern.
 20. The system of claim 17, whereinthe at least one sensor corresponds to an optical coherence tomography(OCT) system configured to determine biometric data associated with thecorrection to be made to the IOL.
 21. The system of claim 17, whereinthe applied laser radiation changes the index of refraction of the atleast one area of the IOL from the first refractive index to thedifferent index of refraction in forming the at least one additionallayer.
 22. The system of claim 17, wherein the index of refraction ofthe formed at least one additional layer is uniform throughout therespective layer.
 23. The system of claim 17, wherein the at least oneadditional layer is formed with a series of transitions within the IOL.24. The system of claim 17, wherein the at least one additional layer isformed to have a shape defined by portions having different depthswithin the IOL.
 25. The system of claim 17, wherein the at least oneadditional layer is formed to have a particular thickness, and wherein,when formed, at least one of the layers has a different thickness thananother one of the layers.